bluuebunny/crossref_metadata_2025_split huggingface dataset:
The next-generation Open Targets Platform: reimagined, redesigned, rebuilt
Authors: Ochoa David , Hercules Andrew , Carmona Miguel , Suveges Daniel , Baker Jarrod , Malangone Cinzia , Lopez Irene , Miranda Alfredo , Cruz-Castillo Carlos , Fumis Luca , Bernal-Llinares Manuel , Tsukanov Kirill , Cornu Helena , Tsirigos Konstantinos , Razuvayevskaya Olesya , Buniello Annalisa , Schwartzentruber Jeremy , Karim Mohd , Ariano Bruno , Martinez Osorio Ricardo Esteban , Ferrer Javier , Ge Xiangyu , Machlitt-Northen Sandra , Gonzalez-Uriarte Asier , Saha Shyamasree , Tirunagari Santosh , Mehta Chintan , Roldán-Romero Juan María , Horswell Stuart , Young Sarah , Ghoussaini Maya , Hulcoop David G , Dunham Ian , McDonagh Ellen M 
Published: November 2022

AbstractThe Open Targets Platform (https://platform.opentargets.org/) is an open source resource to systematically assist drug target identification and prioritisation using publicly available data. Since our last update, we have reimagined, redesigned, and rebuilt the Platform in order to streamline data integration and harmonisation, expand the ways in which users can explore the data, and improve the user experience. The gene–disease causal evidence has been enhanced and expanded to better capture disease causality across rare, common, and somatic diseases. For target and drug annotations, we have incorporated new features that help assess target safety and tractability, including genetic constraint, PROTACtability assessments, and AlphaFold structure predictions. We have also introduced new machine learning applications for knowledge extraction from the published literature, clinical trial information, and drug labels. The new technologies and frameworks introduced since the last update will ease the introduction of new features and the creation of separate instances of the Platform adapted to user requirements. Our new Community forum, expanded training materials, and outreach programme support our users in a range of use cases.
A single-cell human islet interactome atlas identifies disrupted autocrine and paracrine communications in type 2 diabetes
Authors: Bosi Emanuele , Marselli Lorella , Suleiman Mara , Tesi Marta , De Luca Carmela , Del Guerra Silvia , Cnop Miriam , Eizirik Decio L , Marchetti Piero 
Published: November 2022

Abstract
A sensible control of hormone secretion from pancreatic islets requires concerted inter-cellular communications, but a comprehensive picture of the whole islet interactome is presently missing. Single-cell transcriptomics allows to overcome this and we used here a single-cell dataset from type 2 diabetic (T2D) and non-diabetic (ND) donors to leverage islet interaction networks. The single-cell dataset contains 3046 cells classified in 7 cell types. The interactions across cell types in T2D and ND were obtained and resulting networks analysed to identify high-centrality genes and altered interactions in T2D. The T2D interactome displayed a higher number of interactions (10 787) than ND (9707); 1289 interactions involved beta cells (1147 in ND). High-centrality genes included EGFR, FGFR1 and FGFR2, important for cell survival and proliferation. In conclusion, this analysis represents the first in silico model of the human islet interactome, enabling the identification of signatures potentially relevant for T2D pathophysiology.
Pinxian Wang: no place for a ‘gold rush’ in the exploration of the deep sea
Authors: Zhao Weijie , Zhou Zhonghe 
Published: November 2022

Abstract
Prof. Pinxian Wang (汪品先) of Tongji University, born in 1936, is one of the leading deep-sea scientists in China. As the first co-chief scientist of Chinese nationality in the international Ocean Drilling Program (ODP), he co-led ODP Leg 184 in 1999; and in 2018, at 82 years old, he dived to a depth of 1400 meters in the South China Sea (SCS) in China's manned submersible ‘Deep Sea Warrior’. In recent years, he has also become a star of science popularization in China—he has more than 1.7 million followers on China's video-sharing platform bilibili, and his popular science book Deep Sea in Simple Words is a best seller.
In September 2022, Prof. Wang was interviewed by NSR’s Associate Editor-in-Chief, Zhonghe Zhou. In this interview, Prof. Wang summarized his six-decade-long scientific career, talked about the past and future of China's deep-sea research efforts, and explained his opinion on how to promote scientific culture in China.
Safety and Clinical Activity of SHR7390 Monotherapy or Combined With Camrelizumab for Advanced Solid Tumor: Results From Two Phase I Trials
Authors: Wei Xiao-Li , Zhang Yang , Zhao Hong-Yun , Fang Wen-Feng , Luo Hui-Yan , Qiu Miao-Zhen , He Ming-Ming , Zou Ben-Yan , Xie Jie , Jin Chun-Lei , Zhou Xian-Feng , Wang Feng , Wang Feng-Hua , Li Yu-Hong , Wang Zhi-Qiang , Xu Rui-Hua 
Published: November 2022

Abstract

Background
SHR7390 is a novel, selective MEK1/2 inhibitor. Here, we report results from two phase I trials conducted to evaluate the tolerability, safety and antitumor activity of SHR7390 monotherapy for advanced solid tumors and SHR7390 plus camrelizumab for treatment-refractory advanced or metastatic colorectal cancer (CRC).

Patients and Methods
Patients received SHR7390 alone or combined with fixed-dose camrelizumab (200 mg every 2 weeks) in an accelerated titration scheme to determine the maximum tolerated dose (MTD). A recommended dose for expansion was determined based on the safety and tolerability of the dose-escalation stage. The primary endpoints were dose limiting toxicity (DLT) and MTD.

Results
In the SHR7390 monotherapy trial, 16 patients were enrolled. DLTs were reported in the 1.0 mg cohort, and the MTD was 0.75 mg. Grade ≥3 treatment-related adverse events (TRAEs) were recorded in 4 patients (25.0%). No patients achieved objective response. In the SHR7390 combination trial, 22 patients with CRC were enrolled. One DLT was reported in the 0.5 mg cohort and the MTD was not reached. Grade ≥3 TRAEs were observed in 8 patients (36.4%), with the most common being rash (n=4). One grade 5 TRAE (increased intracranial pressure) occurred. Five patients (22.7%) achieved partial response, including one of 3 patients with MSS/MSI-L and BRAF mutant tumors, one of 15 patients with MSS/MSI-L and BRAF wild type tumors, and all 3 patients with MSI-H tumors.

Conclusions
SHR7390 0.5 mg plus camrelizumab showed a manageable safety profile. Preliminary clinical activity was reported regardless of MSI and BRAF status.
Physical Activity Intervention in Patients with Metastatic Breast Cancer During Active Treatment: Quality of Life and Function
Authors: Shachar Shlomit Strulov , Heiling Hillary , Muss Hyman B , Meghan Damone , Wagoner Chad W , Deal Allison M , Nyrop Kirsten A 
Published: November 2022

Abstract

Background
In this study, we explore recruitment, retention, and potential quality of life (QoL) and function benefits from a self-directed, home-based walking intervention in women during active treatment for metastatic breast cancer (MBC).

Methods
In this single-arm pilot study, women with stage IV BC wore an activity tracker (FitbitTM) to measure steps per week throughout the intervention study. Participants were asked to walk 150 min per week at a comfortable and safe pace. Patient-reported outcome measures (PRO) were collected at baseline and follow-up.

Results
Target recruitment of 60 patients was achieved. In 52 patients who completed all baseline measures, mean age was 55 (SD 11.1), 23% were pre-menopausal, and 19% non-White. Forty patients (77%) were retained at 3 months and 29 (56%) at 6 months. Baseline walking was the strongest predictor of retention at 3 months (P = .02). For 24 patients (46%) with analyzable Fitbit data at 3 months, mean steps/week rose from 19,175 to 31,306. Higher number of steps correlated with larger improvements FACT-G General well-being (FACT-G, rho = 0.55, P = .01), FACT-G Physical well-being (rho = 0.48, P = .03), and PROMIS Mental Health (rho = 0.55, P = .01).

Conclusion
Recruitment into a walking intervention is feasible (a priory target of N = 60) in women during treatment for MBC, but retention at 3 months follow-up fell short (77% versus a priori 80%), yet there were potential benefits in general and physical well-being and mental health.

ClinicalTrials.gov Identifier
NCT02682836.
A single-nucleus transcriptomic atlas of primate testicular aging reveals exhaustion of the spermatogonial stem cell reservoir and loss of Sertoli cell homeostasis
Authors: Huang Daoyuan , Zuo Yuesheng , Zhang Chen , Sun Guoqiang , Jing Ying , Lei Jinghui , Ma Shuai , Sun Shuhui , Lu Huifen , Zhang Xiaoli , Cai Yusheng , Zhang Weiqi , Gao Fei , Xiang Andy Peng , Izpisua Belmonte Juan Carlos , Liu Guang-Hui , Qu Jing , Wang Si 
Published: November 2022

Abstract
The testis is pivotal for male reproduction, and its progressive functional decline in aging is associated with infertility. However, the regulatory mechanism underlying primate testicular aging remains largely elusive. Here, we resolve the aging-related cellular and molecular alterations of primate testicular aging by establishing the first single-nucleus transcriptomic atlas. Gene-expression patterns along the spermatogenesis trajectory revealed molecular programs associated with attrition of spermatogonial stem cell reservoir, disturbed meiosis and impaired spermiogenesis along the sequential continuum. Remarkably, Sertoli cell was identified as the cell type most susceptible to aging, given its deeply perturbed age-associated transcriptional profiles. Concomitantly, downregulation of the transcription factor Wilms’ Tumor 1 (WT1), essential for Sertoli cell homeostasis, was associated with accelerated cellular senescence, disrupted tight junctions, and a compromised cell identity signature, which altogether may help create a hostile microenvironment for spermatogenesis. Collectively, our study depicts in-depth transcriptomic traits of non-human primate (NHP) testicular aging at single-cell resolution, providing potential diagnostic biomarkers and targets for therapeutic interventions against testicular aging and age-related male reproductive diseases.
It’s Not the Message, It’s The Messenger: Organizational Identity and White Men’s Opposition to Women’s and African Americans’ Civic Participation
Authors: McVeigh Rory , Carbonaro William , Cannady Emmanuel 
Published: November 2022

AbstractTheories of structural racism and sexism build from an assumption that members of privileged groups react negatively when non-privileged identities link to an agenda for change. We directly test that assumption with three online experiments administered to national samples of white men in the United States. Respondents evaluate web pages of (fictitious) civic organizations displaying agendas that could undermine race and gender hierarchies. We find that in each experiment, respondents are much more likely to disapprove of the organizational identity of the civic organizations if they are evaluating an organization that indicates it is a “Black Alliance,” or a “Women’s Alliance,” rather than simply an “Alliance.” Disapproval of the organizational identity, in turn, differentiates respondents in terms of their levels of support for the organization and its goals. Results across the three experiments are strikingly similar, reflecting the shared micro-level assumption in different macro-level theories.
Lower Versus Higher Exposure to Vasopressor Therapy in Vasodilatory Hypotension: A Systematic Review With Meta-Analysis*
Authors: Richards-Belle Alvin , Hylands Mathieu , Muttalib Fiona , Taran Shaurya , Rochwerg Bram , Day Andrew , Mouncey Paul R. , Radermacher Peter , Couban Rachel , Asfar Pierre , Adhikari Neill K. J. , Lamontagne Francois 
Published: November 2022

OBJECTIVES:
Balancing the risks of hypotension and vasopressor-associated adverse effects is a daily challenge in ICUs. We conducted a systematic review with meta-analysis to examine the effect of lower versus higher exposure to vasopressor therapy on mortality among adult ICU patients with vasodilatory hypotension.

DATA SOURCES:
We searched Ovid Medline, Embase, and the Cochrane Central Register of Controlled Trials for studies published from inception to October 15, 2021.

STUDY SELECTION:
We included randomized controlled trials of lower versus higher exposure to vasopressor therapy in adult ICU patients with vasodilatory hypotension without language or publication status limits.

DATA EXTRACTION:
The primary outcome was 90-day all-cause mortality, with seven prespecified subgroups. Secondary outcomes included shorter- and longer-term mortality, use of life-sustaining therapies, vasopressor-related complications, neurologic outcome, and quality of life at longest reported follow-up. We conducted random-effects meta-analyses to calculate summary effect measures across individual studies (risk ratio [RR] for dichotomous variables, mean difference for continuous variables, both with 95% CIs). The certainty of the evidence was assessed using Grading of Recommendations, Assessment, Development, and Evaluation. We registered this review on the International Prospective Register of Systematic Reviews (CRD42021224434).

DATA SYNTHESIS:
Of 3,403 records retrieved, 68 full-text articles were reviewed and three eligible studies included. Lower exposure to vasopressors probably lowers 90-day mortality but this is based on moderate-certainty evidence, lowered for imprecision (RR, 0.94; 95% CI, 0.87–1.02). There was no credible subgroup effect. Lower vasopressor exposure may also decrease the risk of supraventricular arrhythmia (odds ratio, 0.55; 95% CI, 0.36–0.86; low certainty).

CONCLUSIONS:
In patients with vasodilatory hypotension who are started on vasopressors, moderate-certainty evidence from three randomized trials showed that lower vasopressor exposure probably lowers mortality. However, additional trial data are needed to reach an optimal information size to detect a clinically important 10% relative reduction in mortality with this approach.
Corneal topography and tomography readings with mask wear during the COVID-19 pandemic
Authors: Zein Mike , Wylegala Adam , Sripawadkul Wathanee , Al Bayyat Ghada , Alvarez Osmel P. , Gutierrez Alejandro J. , Guerrero Miguel A. , Galor Anat , Karp Carol L. 
Published: November 2022

Purpose:
To assess the effect of mask wear on corneal topography and tomography readings.

Setting:
Tertiary ophthalmic center.

Design:
Prospective, observational, comparative study.

Methods:
Subjects underwent imaging with the Tomey TMS-4a topographer and the Oculus Pentacam HR tomographer. Imaging was performed without a mask, and then testing was repeated while wearing 3 different masks: Halyard Level 2, Halyard Level 3, and KN95. Measurements during mask wear were compared with measurements without a mask. The Kruskal-Wallis analysis of variance grouped test was used to compare mean differences without vs with mask wear on measurements. The Chi-square test was used to compare frequency of differences between different masks and against-the-rule vs with-the-rule astigmatism. The frequencies of clinically significant changes in axis of astigmatism, magnitude of astigmatism, and mean keratometry (K) values were calculated.

Results:
52 eyes were included in the study with a mean age of 34.71. Mask wear did not show statistically significant differences in mean topography and tomography measurements compared with without mask wear for all parameters. However, the majority, 53% (83/156) had a >10 degrees and 41% (64/156) had >15 degrees change in axis of astigmatism on topography when wearing a mask compared with no mask wear.

Conclusions:
Mask wear did not result in statistically significant mean changes in K readings on topography and tomography. However, the axis of astigmatism varied >10 degrees in most of the patients. Axis determination should be interpreted with caution regarding refractive surgery and/or toric intraocular lens planning in individuals whose measurements were obtained while wearing a mask.
Effect of surgical subcutaneous fat removal on leptin serum concentrations, lipid profile, glucose metabolism, insulin resistance, weight, and body mass index: A Meta-analysis.
Authors: Gómez-Sámano Miguel Ángel , Guerrero-Castillo Anna Paula , Abarca-Arroyo Jorge Antonio , Albuja-González Elena Cristina , García-Bonilla Hans Alessandro , Espinosa-Salazar Héctor Donaldo , Villanueva-Gómez-Crespo María Teresa , Catzin-Kuhlmann Andrés , López-Gatell Hugo , Tlapanco-Beltrán Cristina Aurora , Vera-Zertuche Juan Mauricio , León-Suárez Andrés , Telich-Tarriba José Eduardo , Cuevas-Ramos Daniel , Gómez-Pérez Francisco J , Gulias-Herrero Alfonso 
Published: November 2022

SUMMARY

INTRODUCTION:
Abdominal obesity has been associated with an increased risk of insulin resistance, metabolic syndrome, and diabetes. In contrast, central fat removal procedures like liposuction, lipectomy, and abdominoplasty are among the most common surgical procedures. Nevertheless, the impact of the latter on the former is controversial and understudied.

OBJECTIVE:
to explore the effect of subcutaneous fat elimination procedures on insulin resistance parameters and adipokine levels.

METHODS:
Relevant studies regarding the effects of surgical subcutaneous fat removal on glucose, insulin, adipokines, and lipid metabolism as well as blood pressure, were identified by searching PubMed and Ovid-Cochrane without limits in date, type of publication, or language. After the selection process, 24 studies were obtained. The results of the articles were summarized using descriptive statistics. For the final analysis, a randomized effects model was used to evaluate heterogeneity, averages and meta-analytic differences were expressed with a confidence interval (CI) of 95%.

RESULTS:
All studies reported a reduction in weight (-2.64 kg, 95%CI -4.32, -0.96, p=0.002, i2=36%, p of i2<0.001) and body mass index (BMI) after liposuction. A significant improvement in triglycerides (-10.06 mg/dL, 95%CI -14.03,-6.09, p<0.001, i2=48%, p of i2=0.05), serum glucose concentration (-4.25 mg/dL, 95%CI -5.93,-2.56, p<0.001, i2=68%, p of i2<0.001), serum insulin concentration (-2.86 μIU/mL, 95%CI -3.75,-1.97, p<0.001, i2=59%, p of i2=0.003), and serum leptin concentration (-7.70 ng/mL, 95%CI -11.49,-3.92, p=0.0001, i2=96%, p of i2<0.001) was consistently observed.

CONCLUSIONS:
We do confirm that in addition to weight loss, there is a significant decrease in leptin, triglyceride, glucose, and insulin serum concentrations after liposuction, a fact that should be considered in future discussions.
Quality of Life Improvement Following Blepharoplasty: A Prospective Study
Authors: Papadopulos Nikolaos A. , Archimandritis Theresa , Henrich Gerhard , Kovacs Laszlo , Machens Hans-Günther , Klöppel Markus 
Published: November 2022

Background:
Our previous retrospective study indicates that esthetic surgery in general results in a significant improvement in Quality of life (QoL). This is the first indication-specific prospective evaluation of QoL after blepharoplasty using standardized and validated questionnaires.

Objectives:
To report changes in QoL after blepharoplasty prospectively with a 6-month follow-up.

Methods:
The same surgical team performed an esthetic blepharoplasty on 50 patients. Participants answered 1 set of questionnaires preoperatively and 6 months postoperatively. The instrument consisted of a self-developed indication-specific part specially designed for blepharoplasty and 4 validated and standardized testing instruments (FLZ, FPI-R, RSES, and PHQ-4) with norm data for German-speaking countries available.

Results:
This study reveals a high rate of satisfaction after blepharoplasty. 96% felt better about themselves and 94% would undergo the procedure again. Statistically significant increased values were found postoperatively in the items “income” (P=0.016), “family life” (P=0.028), “partner relationship” (P=0.039), “ability to relax” (P<0.001), “energy” (P<0.001), “hobbies” (P<0.001), and with their outer appearance in general (P=0.018). Blepharoplasty showed a statistically significant improvement in emotional stability (P=0.017) and a reduction in depressive symptoms (P<0.001). Our patients had statistically significantly higher self-esteem before (P<0.001) and after (P<0.001) the intervention.

Conclusion:
Our prospective study shows that blepharoplasty increases most aspects of QoL significantly, has a positive effect on emotional and physical well-being, and reduces the incidence of depressive symptoms and anxiety.
Short-term Outcomes of Laparoscopic and Open Distal Pancreatectomy Using Propensity Score Analysis
Authors: Ota Masato , Asakuma Mitsuhiro , Taniguchi Kohei , Ito Yuri , Komura Kazumasa , Tanaka Tomohito , Yamakawa Kazuma , Ogura Takeshi , Nishioka Daisuke , Hirokawa Fumitoshi , Uchiyama Kazuhisa , Lee Sang-Woong 
Published: November 2022

Objective:
This study aimed to compare the short-term outcomes between laparoscopic and open distal pancreatectomy for lesions of the distal pancreas from a real-world database.

Background:
Reports on the benefits of laparoscopic distal pancreatectomy include 2 randomized controlled trials; however, large-scale, real-world data are scarce.

Methods:
We analyzed the data of patients undergoing laparoscopic or open distal pancreatectomy for benign or malignant pancreatic tumors from April 2008 to May 2020 from a Japanese nationwide inpatient database. We performed propensity score analyses to compare the inhospital mortality, morbidity, readmission rate, reoperation rate, length of postoperative stay, and medical cost between the 2 groups.

Results:
From 5502 eligible patients, we created a pseudopopulation of patients undergoing laparoscopic and open distal pancreatectomy using inverse probability of treatment weighting. Laparoscopic distal pancreatectomy was associated with lower inhospital mortality during the period of admission (0.0% vs 0.7%, P<0.001) and within 30 days (0.0% vs 0.2%, P=0.001), incidence of reoperation during the period of admission (0.7% vs 1.7%, P=0.018), postpancreatectomy hemorrhage (0.4% vs 2.0%, P<0.001), ileus (1.1% vs 2.8%, P=0.007), and shorter postoperative length of stay (17 vs 20 d, P<0.001).

Conclusions:
The propensity score analysis revealed that laparoscopic distal pancreatectomy was associated with better outcomes than open surgery in terms of inhospital mortality, reoperation rate, postoperative length of stay, and incidence of postoperative complications such as postpancreatectomy hemorrhage and ileus.