Melanoma patient data extracted from the TCGA database supports the hypothesis that high MIF expression strongly correlates with poor response to ICB therapy. Our findings provide a rationale for combining anti-CTLA-4 with MIF inhibitors as a potential strategy to overcome resistance to ICB therapy in melanoma, turning a "cold" tumor into a "hot" one mediated by the activation of innate immunity and reprogramming of tumor metabolism and reduced PD-L1 expression in melanoma cells.
HIV transmission from persons unaware of their HIV status occurs more commonly than those who are aware of their status. Knowledge of one's HIV status may encourage preventive behaviors. Anecdotal evidence suggests that many international students may be willing to accept HIV screening, but empirical evidence to support this claim is lacking. We sought to determine the willingness of international students in the United States (US) to accept HIV screening, if offered.

We conducted a cross-sectional study using an online survey of international students at Western Illinois University, USA. The independent variable was the sociodemographic data of our participants; the dependent variable was the acceptance of HIV screening. The covariates were knowledge about HIV and the factors associated with the acceptance of the screening. Descriptive statistics and multivariate analysis were conducted.

A total of 185 respondents out of 491 students participated in the online survey. Of these, 107 (57.8%) were males, and 78 (42.8%) were females. Most of the respondents were from Asian countries (64.9%) and African countries (24.9%). The prevalence of acceptance of HIV screening was 74%. Among participants willing to accept screening, if offered, 90% perceived screening would be beneficial to their health. Meanwhile, 83% of those who would refuse the screening were not sexually active.

Many international students may be interested in getting HIV screening if offered. Awareness of the benefits of HIV screening may influence the decision to screen. Findings may inform further studies that will lead to policy formulations for the health of international students in the US.
Many international students may be interested in getting HIV screening if offered. Awareness of the benefits of HIV screening may influence the decision to screen. Findings may inform further studies that will lead to policy formulations for the health of international students in the US.The ability to create a superlubricious aqueous lubricant is important for various biological and technological applications. Here, a nonlipid biolubricant with strikingly low friction coefficients is fabricated (patented) by reinforcing a fluid-like hydrogel composed of biopolymeric nanofibrils with proteinaceous microgels, which synergistically provide superlubricity on elastomeric surfaces in comparison to any of the sole components. This two-component lubricant composed of positively charged lactoferrin microgels and negatively charged κ-carrageenan hydrogels is capable of exceeding the high lubricating performance of real human saliva in tribo tests using both smooth and textured surfaces, latter mimicking the human tongue's wettability, topography, and compliance. The favorable electrostatic attraction between mutually oppositely charged microgels and the hydrogel reinforces the mechanical properties of the hydrogel, allowing friction reduction by combining the benefits of both viscous and hydration lubrication. The superlubricity of these microgel-reinforced hydrogels offers a unique prospect for the fabrication of biocompatible aqueous lubricants for dry-mouth therapy and/or designing of nonobesogenic nutritional technologies.As clinicians strive to apply evidence-based principles, team-based practitioners have identified a large gap as it relates to published research, ideal applications of evidence-based practice, and actual clinical practice related to injury prevention in elite sport within the United States. For rehabilitation professionals, especially those intimately involved in the research of injury prevention, the solution often seems quite clear and defined. However, preventing injury by implementing the latest recommendation from the most recent prospective study on the using the FIFA 11 + warm-up, a Copenhagen Adduction exercise, or a plyometric drill with elite athletes may not be as effective as was seen among the cohort used in the study. In addition to extrapolating research, clinicians face additional challenges such as variance among professions, schedule density, and off-season contacts with athletes. There is an inherent difficulty in the application of research to practice in elite sport as it relies on the teamwork of not only the practitioner and athlete, but the entire sporting organizational structure and those involved in athlete participation. The purpose of this clinical commentary is to explore the difficulty with application of research in clinical practice and to discuss potential strategies for improving carry over from research to clinical practice.
The number of hip arthroscopies (HAs) performed in the United States is increasing exponentially. Previous authors have shown improvements in short- and mid-term functional outcomes after HA. Despite established overall improvements, functional and objective impairments may persist. In particular, preliminary work demonstrates differences in hip strength between patients who undergo HA when compared to healthy controls at 12- and 24-months post-operative. The purpose of this clinical commentary is to highlight the persistent hip muscle strength and neuromuscular deficits that occur after HA, as well as propose the utilization of neuromuscular electrical stimulation (NMES) as an adjunct to strengthening exercises in early post-operative rehabilitation to address deficits.

Arthrogenic muscle inhibition (AMI), drives neuromuscular dysfunction and has been shown to occur in peripheral joints. https://www.selleckchem.com/products/sgc-0946.html The knee and hip have historically benefited from NMES to aid in improved muscular function, such as in those who haveition. Ultimately, these strategies could produce improved outcomes guided by robust evidence-based protocols.

5.
5.

Significant differences were found in the mean of all the T
, T
, PD, and ADC values between high- and low-grade BCa. The best diagnostic performance was found for the mean ADC value with an area under the ROC curve (AUC) of 0.869, while the AUC values of the mean PD, T
, and T
values were 0.755, 0.740, and 0.723, respectively.

SyMRI may be a potential noninvasive technique for evaluating the histological grade of BCa. However, the overall diagnostic performance of SyMRI-derived parameters was inferior to the ADC value.

2.

2.
2.
The Ibn Rochd CHU is a tertiary care structure that provides care for the most severe cases of COVID-19 requiring hospitalisation in intensive care. The objective of study is to describe the complementary medical and psychological care of patients with COVID-19 in the endocrinology department after a stay in intensive care.

This is a descriptive observational study of patients transferred from the intensive care unit to the endocrinology service following a COVID-19 infection during the period from 17 April 2020 to May 26, 2020. Clinical characteristics of the patients and complications related to COVID-19 infection were studied; a nutritional assessment using the MNA nutritional status assessment questionnaire; psychological assessment using quality-of-life questionnaires (Hamilton depression and anxiety, HAD, SF36, PCLS); a treatment satisfaction questionnaire (TQCMII) and an assessment of patient autonomy by the ADL score.

Our study included 41 patients with an average age of 55years (19-85years), a plications from coronavirus infection, vulnerable to undernutrition, psychological and motor complications. Additional care before discharge is essential for better integration of patients into their families.
Globally, hypertension is a major concern in all health care systems. The role of clinical pharmacists in managing hypertension is essential not only in dispensing drugs but also in actively participating in managing treatment regimens. The goal of this study was to support the role of clinical pharmacists in managing patient hypertension therapy.

This study was designed as a pragmatic, prospective, quasi-experimental study. In this study, 160 patients were enrolled, but seven patients withdrew from the study. The effects of the intervention were studied on the remaining 153 participants. Blood pressure, MINICHAL score, and DAI-10 score were measured at the beginning and at the end of the study. The patients received different medication counselling sessions that included medication education. The counselling sessions were conducted three times, with each session 4months apart from the previous session. The first session was conducted at the beginning of the study following the enrolment of the patients. in the health care system.
The interventions of clinical pharmacists were found to be significantly important in improving the outcomes of hypertensive patients. Therefore, legislation making clinical pharmacy services compulsory in Middle Eastern health care systems, and particularly the UAE, is needed to expand the roles of pharmacists within the health care system.
Cosmos caudatus (CC) is traditional Asian vegetable, commonly consumed among the Southeast Asian population. It has been reported to be high in flavonoids and might potentially improve brain activity among older adults with mild cognitive impairment (MCI). The effect of CC in brain activation improvement using neuroimaging is yet to be discovered.

To investigate the effects of CC supplement on brain activity using functional magnetic resonance imaging (fMRI) among older adults with MCI.

Prospective, randomized, double-blind, placebo-controlled trial.

Twenty older adults with mild cognitive impairment (60-75 years old), 14 of them (70%) were female subjects.

A 3.0-T, T1-weighted anatomical images, T2*-weighted imaging data, A single shot, gradient echo-echo planar imaging (EPI) sequence.

All subjects were asked to consume two 500 mg capsules of either CC supplement or placebo (maltodextrin) daily for 12 weeks. Cognitive function was measured using validated neuropsychological tests (i.e. Mini-mentaally leading to improved working memory among older adults with MCI after 12 weeks of administration.

1 TECHNICAL EFFICACY Stage 4.
1 TECHNICAL EFFICACY Stage 4.The Nigerian Ministry of Health has been offering care for noma patients for many years at the Noma Children's Hospital (NCH) in Sokoto, northwest Nigeria, and Médecins Sans Frontières has supported these initiatives since 2014. The comprehensive model of care consists of four main components acute care, care for noma sequelae, integrated hospital-based services and community-based services. The model of care is based on the limited evidence available for prevention and treatment of noma and follows WHO's protocols for acute patients and best practice guidelines for the surgical treatment of noma survivors. https://www.selleckchem.com/products/alkbh5-inhibitor-2.html The model is updated continually as new evidence becomes available, including evidence generated through the operational research studies performed at NCH. By describing the model of care, we wish to share the lessons learned with other actors working in the noma and neglected tropical disease sphere in the hope of guiding programme development.
In this study, it is aimed to identify the rate of successful placement of a guidewire down through the ureter during PNL and to compare the outcomes of different locations of guidewires in the collecting system following renal puncture in terms of success and complications rates.

Data of 1052 patients who underwent miniPNL in our institution between January 2014 and November 2020 were analysed. Patients were divided into three groups. Group I consisted of patients with the guidewire coiled within the punctured calyx, group II consisted of patients with the guidewire reaching the renal pelvis and group III consisted of patients with the guidewire passed down through the ureter. The groups were compared for successful tract creation and complication rates.

There were 303 (28.8%) patients in group I, 330 (31.4%) patients in group II and 419 (39.8%) patients in group III. Successful tract dilation at the first attempt was established in 298 (94.7%) patients in group I, 328 (99.4%) patients in group II and in all of the 419 (100%) patients in group III.

Reciprocity is a fundamental mechanism for sustained social relationships. Escalation-based theories suggest that reciprocity intensifies over time. In contrast, equity-based theories propose that people reciprocate behaviors in kind. We reconcile these conflicting perspectives by examining social exchanges across different cultural contexts. Using three complementary experiments, we investigate when, how, and why individuals in East Asian settings and those in North American settings differentially reciprocate positive versus negative behaviors over time. Study 1 demonstrated that in positively framed exchanges (i.e., giving) Americans escalated their reciprocity, but Singaporeans reciprocated in kind. However, in negatively framed exchanges (i.e., taking), Singaporeans escalated their reciprocity, but Americans reciprocated in kind. Study 2 replicated the results using Hong Kongers and showed that cultural differences in regulatory focus were associated with specific emotions (i.e., anxiety and happiness), which then escalated reciprocity. To establish causality, Study 3 manipulated regulatory focus within one culture and replicated the pattern of results.The first year represents an exceptional time of development during which important social skills emerge, like action and emotion understanding. However, to date, no study explored the neural underpinnings of infants' ability to bind emotion- to action-related information. To assess this issue, we measured EEG activity while 6-month-old infants observed the same action performed by an actress displaying three different emotional expressions (happiness, anger and neutral). Results have shown that actions embedded in an emotional context (happiness and anger) elicited larger early negativity at parieto-occipital sites compared to a neutral context. This finding suggests that already at 6 months of age, infants use information coming from facial expressions to detect the saliency and relevance of others' actions.A surveillance study was performed in an intensive care unit in the largest tertiary health care center in Vojvodina, Serbia from 2014 to 2018. Antibiotic prescription data were collated in the WHO anatomical therapeutic chemical (ATC)/defined daily dose (DDD) format, while antibiotic resistance was expressed as incidence density adjusted for total inpatient-days. https://www.selleckchem.com/products/ve-821.html Individual trends were determined by linear regression, while possible associations between antibiotic prescription and resistance were evaluated using cross-correlation analysis. An overall decrease in antibiotic utilization was observed. The prescription rates of piperacillin-tazobactam increased significantly, while consumption of 3rd and 4th generation cephalosporins and fluoroquinolones decreased. There were rising incidence densities of doripenem resistant Acinetobacter spp., piperacillin-tazobactam resistant Pseudomonas aeruginosa and carbapenem and colistin resistant Klebsiella pneumoniae. These results can serve as a basis for the development of antimicrobial stewardship strategies in the current setting.Purpose To report a technique of global cerebral embolic protection (CEP) designed for use during thoracic endovascular aortic repair (TEVAR). Technique Arterial cannulas are inserted percutaneously in the right axillary artery (12-F) and left common carotid artery (LCCA; 10-F) to provide normothermic antegrade cerebral perfusion during TEVAR with neuromonitoring. Inferior vena cava blood is drawn using a 19-F femoral cannula, filtered, oxygenated, and delivered through independent roller pumps to the arterial cannulas. Static CEP is obtained by balloon occlusion of the 3 aortic arch branches proximally, resulting in complete separation of aortic and cerebral blood flow; static CEP is used during aortic endograft delivery and deployment. Dynamic CEP, obtained by creating flow reversal in the innominate artery and proximal LCCA, is used at all other times. Successful use of this CEP technique is illustrated in a patient with shaggy aorta undergoing fenestrated total arch TEVAR. Conclusion Percutaneous normothermic bilateral antegrade cerebral perfusion provides effective CEP during TEVAR.Axon bifurcation - a specific form of branching of somatosensory axons characterized by the splitting of the growth cone - is mediated by a cGMP-dependent signaling cascade composed of the extracellular ligand CNP (C-type natriuretic peptide), the transmembrane receptor guanylyl cyclase Npr2 (natriuretic peptide receptor 2), and the kinase cGKI (cGMP-dependent protein kinase I). In the absence of any one of these components, the formation of T-shaped axonal branches is impaired in neurons from DRGs (dorsal root ganglia), CSGs (cranial sensory ganglia) and MTNs (mesencephalic trigeminal neurons) in the murine spinal cord or hindbrain. Instead, axons from DRGs or from CSGs extend only either in an ascending or descending direction, while axons from MTNs either elongate within the hindbrain or extend via the trigeminal ganglion to the masseter muscles. Collateral formation from non-bifurcating stem axons is not affected by impaired cGMP signaling. Activation of Npr2 requires both binding of the ligand CNP as well as phosphorylation of serine and threonine residues at the juxtamembrane regions of the receptor. The absence of bifurcation results in an altered shape of termination fields of sensory afferents in the spinal cord and resulted in impaired noxious heat sensation and nociception whereas motor coordination appeared normal.This study examined the relationship between drug use and violence victimization among incarcerated women in Appalachian Kentucky. The purpose of this study was to test the utility of Goldstein's tripartite conceptual framework among rural incarcerated women, by examining whether distinct drugs/violence nexus groups could be classified based on psychopharmacological, economic-compulsive, and systemic factors. This study used secondary data from a National Institute on Drug Abuse (NIDA)-funded grant focused on risk reduction among high-risk incarcerated women in Appalachia (N = 400). Predicted drugs/violence groups were developed using a series of discriminant function analyses. The data yielded three statistically significant discriminant models. Findings of the classified groupings indicated support for three distinct drugs/violence victimization subgroups. The psychopharmacological group showed the greatest prevalence (n = 181; Wilks's λ = .389, F = 3.94, p less then .001), followed by the economic-compulsive group (n = 77; Wilks's λ = .

The study reflects that many HPs in EDs participated in and are familiar with FPDR, with the majority of ED physicians supporting it. Further studies should investigate the reasons for the lack of support from nurses. Results may contribute to the development of hospital ED policies that allow FPDR in the region.
The study reflects that many HPs in EDs participated in and are familiar with FPDR, with the majority of ED physicians supporting it. Further studies should investigate the reasons for the lack of support from nurses. Results may contribute to the development of hospital ED policies that allow FPDR in the region.
It is unclear if the
Tc-sodium phytate (
Tc-SP) is as reliable as the gold-standard
Tc-sulfur colloid (
Tc-SC) for gastric emptying scintigraphy (GES). This study is aimed to compare the emptying rates of both radiotracers in a prospective, randomized cross-over trial and to determine the normative data of a healthy multi-ethnic Asian population.

Out of the 44 healthy individuals screened, 31 (14 females; mean age 28.4 ± 7.0 years) were enrolled and underwent GES using the standardized egg-white meal. All participants were randomly assigned to either
Tc-SP or
Tc-SC on the first GES session before crossed over to the other formulation after 2 weeks.

Both kits achieved the radiochemical purities of > 95%. The median rate (95th upper normative limit) of gastric emptying, reported as total gastric meal retention between
Tc-SP and
Tc-SC, was found to be comparable at all measured time points 0.5 h [85.0% (96.6%) vs. 82.0% (94.0%)], 1 h [70.0% (86.4%) vs. 65.0% (86.6%)], 2 h [31.0% (55.8%) vs ).
Maternal poliovirus antibodies could provide passive immunity to the newborns from poliovirus infection during their first few months of life, but they may impair the immune responses of infants to the poliovirus vaccine as well. In our study, we pooled the data from three clinical trials of the inactivated poliovirus vaccine (IPV) based on Sabin strains to investigate the effect of maternal poliovirus antibodies on the immune responses of infants to poliovirus vaccines.

There were five groups in the pooled analysis, including low-dose Sabin IPV, medium-dose Sabin IPV, high-dose Sabin IPV, control Sabin IPV, and control Salk IPV groups. We reclassified the infants in different groups according to their maternal poliovirus antibodies by two methods, the first one included maternal antibody negative (< 18) and maternal antibody positive (≥18), and the second one included maternal antibody titer < 18, 18 ~ < 132 and ≥ 132. Then, we compared the geometric mean titers (GMTs), geometric mean antibody fnd 18 ~ < 132.

Maternal poliovirus antibodies interfered with the immune responses of infants to poliovirus vaccines, and a high level of maternal antibodies exhibited a greater dampening effect.

ClinicalTrials.gov NCT04264598 February 11, 2020; ClinicalTrials.gov NCT04264546 February 11, 2020; ClinicalTrials.gov NCT03902054 April 3, 2019. Retrospectively registered.
ClinicalTrials.gov NCT04264598 February 11, 2020; ClinicalTrials.gov NCT04264546 February 11, 2020; ClinicalTrials.gov NCT03902054 April 3, 2019. Retrospectively registered.
Alström syndrome is a rare recessively inherited disorder caused by variants in the ALMS1 gene. It is characterized by multiple organ dysfunction, including cone-rod retinal dystrophy, dilated cardiomyopathy, hearing loss, obesity, insulin resistance, hyperinsulinemia, type 2 diabetes mellitus and systemic fibrosis. Heterogeneity and age-dependent development of clinical manifestations make it difficult to obtain a clear diagnosis, especially in pediatric patients.

Here we report the case of a girl with Alström syndrome. Genetic examination was proposed at age 22 months when suspected macular degeneration was the only major finding. Next generation sequencing of a panel of genes linked to eye-related pathologies revealed two compound heterozygous variants in the ALMS1 gene. Frameshift variants c.1196_1202del, p.(Thr399Lysfs*11), rs761292021 and c.11310_11313del, (p.Glu3771Trpfs*18), rs747272625 were detected in exons 5 and 16, respectively. Both variants cause frameshifts and generation of a premature stop-codon that probably leads to mRNA nonsense-mediated decay. Validation and segregation of ALMS1 variants were confirmed by Sanger sequencing.

Genetic testing makes it possible, even in childhood, to increase the number of correct diagnoses of patients who have ambiguous phenotypes caused by rare genetic variants. The development of high-throughput sequencing technologies offers an exceptionally valuable screening tool for clear genetic diagnoses and ensures early multidisciplinary management and treatment of the emerging symptoms.
Genetic testing makes it possible, even in childhood, to increase the number of correct diagnoses of patients who have ambiguous phenotypes caused by rare genetic variants. The development of high-throughput sequencing technologies offers an exceptionally valuable screening tool for clear genetic diagnoses and ensures early multidisciplinary management and treatment of the emerging symptoms.
Long non-coding RNAs (lncRNAs) are involved in many fundamental biological processes, such as transcription regulation, protein degradation, and cell differentiation. Information on lncRNA in the melon fly, Zeugodacus cucurbitae (Coquillett) is currently limited.

We constructed 24 RNA-seq libraries from eight tissues (midgut, Malpighian tubules, fat body, ovary, and testis) of Z. cucurbitae adults. https://www.selleckchem.com/products/mk-4827.html A total of 3124 lncRNA transcripts were identified. Among those, 1464 were lincRNAs, 1037 were intronic lncRNAs, 301 were anti-sense lncRNAs, and 322 were sense lncRNAs. The majority of lncRNAs contained two exons and one isoform. Differentially expressed lncRNAs were analyzed between tissues, and Malpighian tubules versus testis had the largest number. Some lncRNAs exhibited strong tissue specificity. Specifically expressed lncRNAs were identified and filtered in tissues of female and male Z. cucurbitae based on their expression levels. Four midgut-specific lncRNAs were validated by quantitative real-time polymerase chain reaction (RT-qPCR), and the data were consistent with RNA-seq data.

To evaluate the dosimetric and image-guided radiation therapy (IGRT) performance of a novel generative adversarial network (GAN) generated synthetic CT (synCT) in the brain and compare its performance for clinical use including conventional brain radiotherapy, cranial stereotactic radiosurgery (SRS), planar, and volumetric IGRT.

SynCT images for 12 brain cancer patients (6 SRS, 6 conventional) were generated from T1-weighted postgadolinium magnetic resonance (MR) images by applying a GAN model with a residual network (ResNet) generator and a convolutional neural network (CNN) with 5 convolutional layers as the discriminator that classified input images as real or synthetic. Following rigid registration, clinical structures and treatment plans derived from simulation CT (simCT) images were transferred to synCTs. Dose was recalculated for 15 simCT/synCT plan pairs using fixed monitor units. Two-dimensional (2D) gamma analysis (2%/2mm, 1%/1mm) was performed to compare dose distributions at isocenter. Dose-vorain cancer therapy.
Brain GAN synCTs demonstrated excellent performance for dosimetric and IGRT endpoints, offering potential use in high precision brain cancer therapy.The outer membrane of a Gram-negative bacterium is a crucial barrier between the external environment and its internal physiology. This barrier is bridged selectively by β-barrel outer membrane proteins (OMPs). The in vivo folding and biogenesis of OMPs necessitates the assistance of the outer membrane chaperone BamA. Nevertheless, OMPs retain the ability of independent self-assembly in vitro. Hence, it is unclear whether substrate-chaperone dynamics is influenced by the intrinsic ability of OMPs to fold, the magnitude of BamA-OMP interdependence, and the contribution of BamA to the kinetics of OMP assembly. We addressed this by monitoring the assembly kinetics of multiple 8-stranded β-barrel OMP substrates with(out) BamA. We also examined whether BamA is species-specific, or nonspecifically accelerates folding kinetics of substrates from independent species. Our findings reveal BamA as a substrate-independent promiscuous molecular chaperone, which assists the unfolded OMP to overcome the kinetic barrier imposed by the bilayer membrane. We additionally show that while BamA kinetically accelerates OMP folding, the OMP primary sequence remains a vital deciding element in its assembly rate. Our study provides unexpected insights on OMP assembly and the functional relevance of BamA in vivo.Asian Citrus Psyllid (ACP), Diaphorina citri, is a key vector transmitting the causative agent of Huanglongbing (HLB) disease. Population growth of ACP is evident after feeding on plant flush shoots, as they only oviposit here. However, the underlying mechanism as to why flush shoots govern oviposition is unclear. https://www.selleckchem.com/products/SB-202190.html This study compares the fecundity and ovarian morphology of ACP between young flush and mature leaves. Furthermore, the transcriptome of mated females infesting Murraya paniculata was analysed. Finally, the gene of the key Target of Rapamycin (TOR) signalling pathway was silenced by RNAi. Results indicated that flush shoot feeding activated the development of the psyllids ovary and therefore induced oviposition. A total of 126 and 2794 differentially expressed genes were detected at 1 and 5 days, respectively, after pest infestation of flush shoots compared to mature leaves. Many genes are involved in protein metabolism, Mitogen-Activated Protein Kinase (MAPK) signalling pathway, hormone synthesis, and TOR signalling pathway all thought to activate reproduction. Silencing of the positive regulator gene DcRheb in the TOR pathway resulted in lower levels of ecdysone and juvenile hormone and decreased vitellogenin synthesis, further disrupting reproductive ability. This study enhances understanding of the molecular mechanism underlying ACP's reproductive strategy.Langerhans cell sarcoma (LCS) is a high-grade neoplasm with overtly malignant cytological features and a Langerhans cell phenotype. The underlying genetic features are poorly understood, and only a few alterations, such as those of the MARK pathway-related genes, CDKN2A and TP53 have been reported. Here we present a 70-year-old male with LCS on the scalp and pulmonary metastasis. The multinodular tumor, 3.0 cm in diameter, consisted of diffusely proliferated pleomorphic cells with numerous mitoses (53/10 HPFs). Immunohistochemically, the tumor cells were positive for CD1a, Langerin and PD-L1, and the Ki-67 labeling index was 50%. These pathological features were consistent with LCS, and were also observed in the metastatic tumor. Whole-exome sequencing revealed that both the primary and metastatic tumors harbored a large number of mutations (>20 mutations/megabase), with deletion of CDKN2A and TP53 mutation, and highlighted that the mutational signature was predominantly characteristic of ultraviolet (UV) exposure (W = 0.828). Our results suggest, for the first time, that DNA damage by UV could accumulate in Langerhans cells and play a role in the pathogenesis of LCS. The high mutational burden and PD-L1 expression in the tumor would provide a rationale for the use of immune checkpoint inhibitors for treatment of unresectable LCS.
This single-center comparative randomized superiority study compared biliary stenting using fully covered self-expandable metal stents (FCSEMS) and biliary stenting using plastic stents (PS) in preoperative biliary drainage of patients with borderline resectable pancreatic cancer (BRPC) who are planned to undergo a single regimen of neo-adjuvant chemotherapy (NAC).

Twenty-two patients with BRPC who required preoperative biliary drainage before NAC (Gemcitabine plus Nab-paclitaxel) were randomly assigned 11 to the FCSEMS or PS group. The primary endpoint was the rate of stent dysfunction until surgery or tumor progression. Secondary endpoints were stent patency, number of re-interventions, adverse events of endoscopic retrograde biliary drainage (EBD), operation time, volume of intraoperative bleeding, postoperative hospitalization, postoperative adverse events and medical costs.

Eleven patients in each of the groups reached the primary endpoint. The FCSEMS group showed a significantly lower rate of stent dysfunction (18.