bluuebunny/crossref_metadata_2025_split huggingface dataset:
90 Nakajo-Nishimura syndrome: a case report
Authors: Halima Zerguine , Hadef Djohra , Soltani Hanane , Zerrouki Younes , Ouazani Sana , Belkacemi Hafidha , Challa Safia , Slimani Samy 
Published: October 2022

Abstract

Introduction
Nakajo-Nishimura is a rare autosomal recessive inherited autoinflammatory condition that has been described mainly in the Japanese population, but very similar syndromes, such as Candle syndrome, have been reported in Western populations. There is no gold standard treatment for this condition. This is a case report of a 12-year-old female who most likely has Nakajo-Nishimura syndrome.

Methods and results
A 12-year-old female (born in 2010), from Batna (Algeria), was born of a first-degree consanguineous marriage, and the second of two children. She had no relevant past medical history. She was referred on account of dermatology symptoms, occurring very early in life, with papules and distal purplish erythema located in fingers and toes associated with an acrocyanosis. Subsequently, diffuse arthralgias appeared, exacerbated by cold, with a delay in walking, around the age of 3 years.
Clinical examination revealed a thread-like appearance of the fingers with shortening of the 5th digit, and small erythematous lesions, without sclerosis or Raynaud's disease. There was no sign of synovitis or joint deformities. Hepatosplenomegaly with dental dysgenesis and delayed puberty were noted. The laboratory tests showed an inflammatory syndrome—ESR (Erythrocyte Sedimentation Rate) of 100 mm the first h, positive CRP (C-reactive protein), hyper alpha and gamma globulinaemia, and inflammatory anaemia with thrombocytopaenia. The genetic work-up is currently in progress.
The treatment was Hydroxychloroquine and steroids. After the onset of a nephrotic syndrome, Mycophenolate mofetil (MMF) was added. The renal biopsy found a renal amyloidosis. The patient was in chronic renal failure stage 4 requiring hemodialysis.

Conclusion
Extremely rare syndrome described in 30 patients in the literature and whose treatment remains symptomatic and does not prevent complications.

Disclosure of Interest
None declared
Diversity in MD–PhD Programs and Factors Affecting Admission and Completion Among Minoritized Groups: A Scoping Review
Authors: Cavanagh Alice , Owais Sawayra , Syed Saad A. , Zhang Ali , Van Lieshout Ryan J. 
Published: October 2022

Purpose
To improve awareness of diversity in MD–PhD program applicants, matriculants, and graduates; facilitators and barriers to matriculation and/or completion among minoritized groups; and the effects of research experience programs on admissions processes aimed to increase representation of minoritized groups in MD–PhD programs.

Method
The authors conducted a scoping review, searching EMBASE, MEDLINE, PsycINFO, CINAHL, and Web of Science through December 21, 2021, for studies that contained data on the characteristics of MD–PhD learners and initiatives aimed to make the clinician–scientist trainee population more diverse. They excluded studies that had no primary data, were unavailable in English, and were not peer-reviewed.

Results
Of 4,369 articles identified, 16 met inclusion criteria. Studies conceptualized diversity inconsistently, including as sex/gender disparities (n = 11), race/ethnicity underrepresentation (n = 9), disability (n = 2), first-generation student (n = 1), visible minority (n = 1), Indigenous population (n = 1), and economic/social disadvantage (n = 1). Potential barriers to entering or continuing in an MD–PhD program among women and underrepresented ethnic minorities included the long program duration and lack of mentorship; potential facilitators included the flexibility of the dual-degree program. Limited data on high school, undergraduate, and postbaccalaureate research experience programs targeting underrepresented minorities suggest that they may help facilitate admission into MD–PhD programs.

Conclusions
The findings of this scoping review suggest that the diversity of MD–PhD students has been conceptualized in unitary, inconsistent terms, without addressing how different dimensions of diversity may intersect and impact MD–PhD admissions. Future studies should be explicit and intentional in defining “diversity” as it relates to their research questions, explore the impact of intersectionality, and systematically identify and address causal facilitators and barriers of entry to and completion of MD–PhD programs among minoritized groups.
Thoracic radiotherapy may improve the outcome of extensive stage small cell lung carcinoma patients treated with first-line immunotherapy plus chemotherapy
Authors: Wu Jia-Jun , Huang Jing-Wen , Hsu Kuo-Hsuan , Huang Yen-Hsiang , Chen Kun-Chieh , Tseng Jeng-Sen , Yang Tsung-Ying , Chang Gee-Chen 
Published: October 2022

Objective
Immunotherapy plus etoposide and platinum (EP)-based chemotherapy is the standard of care for patients with extensive stage–small cell lung carcinoma (ES-SCLC). In the era of immunotherapy, the role of thoracic radiotherapy for ES-SCLC remains unclear.

Methods
We retrospectively included ES-SCLC patients treated with first-line EP-based chemotherapy plus atezolizumab or durvalumab at Taichung Veterans General Hospital to evaluate the prognostic role and safety of thoracic radiotherapy.

Results
A total of 22 patients were included. The median age was 64 years and most of them were male and smokers. Sixteen patients (72.7%) received durvalumab, while the other 6 patients (27.3%) underwent atezolizumab treatment. Among these patients, 11 (50.0%) had a history of thoracic radiotherapy. There was no significant difference in baseline characteristics between patients with and without thoracic radiotherapy. In the overall population, the objective response rate to immunotherapy plus chemotherapy was 73.7%. The progression-free survival and overall survival were 6.0 months (95% CI: 4.0–7.9) and 13.8 months (95% CI: 8.0–19.6), respectively. The overall survival was significantly longer in patients with thoracic radiotherapy (not-reached [NR] [95% CI NR-NR] vs. 9.6 months [95% CI 2.5–16.6]), respectively (P value by log-rank test <0.001). Both multivariate analysis and subgroup analysis specifically comparing patients with consolidative thoracic radiotherapy and patients with clinical benefits to systemic therapy who did not undergo thoracic radiotherapy indicated that thoracic radiotherapy improved survival.

Conclusion
The real-world efficacy of EP-based chemotherapy plus atezolizumab or durvalumab was comparable with that of clinical trials. Thoracic radiotherapy may improve the outcome of ES-SCLC.
Long-Term Maintenance of Cardiorespiratory Fitness Gains After Cardiac Rehabilitation Reduces Mortality Risk in Patients With Multimorbidity
Authors: Ozemek Cemal , Arena Ross , Rouleau Codie R. , Campbell Tavis S. , Hauer Trina , Wilton Stephen B. , Stone James , Laddu Deepika , Williamson Tamara M. , Liu Hongwei , Chirico Daniele , Austford Leslie D. , Aggarwal Sandeep 
Published: October 2022

Purpose:
The objective of this study was to characterize the impact of multimorbidity and cardiorespiratory fitness (CRF) on mortality in patients completing cardiac rehabilitation (CR).

Methods:
This cohort study included data from patients with a history of cardiovascular disease (CVD) completing a 12-wk CR program between January 1996 and March 2016, with follow-up through March 2017. Patients were stratified by the presence of multimorbidity, which was defined as having a diagnosis of ≥2 noncommunicable diseases (NCDs). Cox regression analyses were used to evaluate the effects of multimorbidity and CRF on mortality in patients completing CR. Symptom-limited exercise tests were completed at baseline, immediately following CR (12 wk), with a subgroup completing another test at 1-yr follow-up. Peak metabolic equivalents (METs) were determined from treadmill speed and grade.

Results:
Of the 8320 patients (61 ± 10 yr, 82% male) included in the analyses, 5713 (69%) patients only had CVD diagnosis, 2232 (27%) had CVD+1 NCD, and 375 (4%) had CVD+≥2 NCDs. Peak METs at baseline (7.8 ± 2.0, 6.9 ± 2.0, 6.1 ± 1.9 METs), change in peak METs immediately following CR (0.98 ± 0.98, 0.83 ± 0.95, 0.76 ± 0.95 METs), and change in peak METs 1 yr after CR (0.98 ± 1.27, 0.75 ± 1.17, 0.36 ± 1.24 METs) were different (P < .001) among the subgroups. Peak METs at 12 wk and the presence of coexisting conditions were each predictors (P < .001) of mortality. Improvements in CRF by ≥0.5 METS from baseline to 1-yr follow-up among patients with or without multimorbidity were associated with lower mortality rates.

Conclusion:
Increasing CRF by ≥0.5 METs improves survival regardless of multimorbidity status.
Blood pressure reduction cut-points for orthostatic hypotension in stroke survivors using a sit-up test: a multicentre cross-sectional study
Authors: Oyake Kazuaki , Tateishi Takaki , Murayama Jun , Shijima Naoki , Sekizuka Tasuku , Otaka Yohei , Momose Kimito 
Published: October 2022

Objective:
The sit-up test is used to assess orthostatic hypotension in stroke survivors who cannot stand independently without using a tilt table. However, no study has identified the optimal cut-points for orthostatic hypotension using the test. Therefore, this study aimed to examine the decrease in SBP and DBP during the sit-up test to detect orthostatic hypotension in individuals with stroke.

Methods:
Thirty-eight individuals with stroke, recruited from three convalescent rehabilitation hospitals, underwent the sit-up and head-up tilt tests. Systolic and diastolic orthostatic hypotension was defined as a decrease of at least 20 and 10 mmHg in the SBP and DBP, respectively, during the head-up tilt test. The receiver operator characteristic curve with the Youden Index was used to identify the optimal cut-points.

Results:
Eight and three participants showed systolic and diastolic orthostatic hypotension, respectively. The optimal cut-points for orthostatic hypotension using the sit-up test were a decrease of 10 mmHg in SBP [sensitivity = 87.5% (95% confidence interval: 47.4–99.7), specificity = 96.7% (82.8–99.9)] and 5 mmHg in DBP [sensitivity = 100.0% (29.2–100.0), specificity = 88.6% (73.3–96.8)].

Conclusion:
Compared with the conventional cut-points, smaller cut-points of a decrease in SBP and DBP may be better to identify orthostatic hypotension in individuals with stroke using the sit-up test. The findings of this study may provide valuable information for the clinical application of the sit-up test.
Serum parabens and its correlations with immunologic and cellular markers in Southern Taiwan industrialized city systemic lupus erythematosus patients
Authors: Huang Kun-Siang , Chen Chun-Yu , Sun Chiao-Yin , Su Yu-Jih 
Published: October 2022

Background:
Although the immune systems of patients with systemic lupus erythematosus (SLE) are affected by both personal characteristics and environmental factors, the effects of parabens on patients with SLE have not been well studied. We investigated the indirect effects of four parabens—methylparaben (MP), ethylparaben (EP), propylparaben (n-PrP), and butylparaben (n-BuP)—on several immunological markers.

Methods:
We assessed the serum levels of MP, EP, n-PrP, and n-BuP in 25 SLE patients and correlated the concentration of each paraben with available clinical and laboratory markers, including intracellular markers of antiviral immunity and apoptosis.

Results:
The expression of aryl hydrocarbon receptor (AhR) was significantly negatively correlated with n-PrP levels (p = 0.03, r = −0.434). In monocytes, APO2.7 was significantly positively correlated with n-BuP levels (p = 0.019, r = 0.467). Glutathione levels were significantly negatively correlated with n-BuP levels (p = 0.019, r = −0.518). Anti- β2 glycoprotein I IgM was significantly positively correlated with both MP (p = 0.011, r = 0.585) and EP levels (p = 0.032, r = 0.506). Anti–cardiolipin IgA was significantly positively correlated with both MP (p = 0.038, r = 0.493) and n-PrP levels (p = 0.031, r = 0.508). On CD8 T cells, the early apoptotic marker annexin V was significantly negatively correlated with both MP (p < 0.05, r = −0.541) and n-BuP levels (p = 0.02, r = −0.616), and L-selectin was significantly positively correlated with both MP (p < 0.05, r = 0.47) and n-PrP levels (p = 0.02, r = 0.556).

Conclusion:
Our findings suggest that higher parabens levels were associated with lower AhR expression in leukocytes, increased monocyte apoptosis, lower serum glutathione levels, reduced annexin V expression on CD8 T cells, and higher L-selectin levels on leukocytes.
Recent Apolipoprotein CIII trials
Authors: Tramontano Daniele , Bini Simone , D’Erasmo Laura , Arca Marcello 
Published: October 2022

Purpose of review
This review will briefly revise the evidence concerning the pharmacological inhibition of Apolipoprotein CIII (ApoCIII) in patients with hypertriglyceridemia.

Recent findings
ApoCIII is a plasma apolipoprotein playing a major role in the metabolism of triglyceride-rich lipoproteins, namely chylomicrons and very-low-density lipoproteins as well as in the pathological processes involved in atherosclerosis. Therefore, ApoCIII is a potential new target for reducing plasma levels of TRLs and, thereby, cardiovascular risk. In recent years, there have been extensive preclinical and clinical pharmacological studies aimed at testing drugs directed against ApoCIII.

Summary
In this review, firstly we will summarize the molecular function of ApoCIII in lipoprotein metabolism. Then, we will examine the lipid-lowering potential of the pharmacological inhibition of ApoCIII based on the results of clinical trial employing Volansesorsen, the first approved antisense therapeutic oligonucleotide against ApoCIII mRNA. The future perspectives for ApoCIII inhibition will be also revised.
New algorithms for treating homozygous familial hypercholesterolemia
Authors: Tromp Tycho R. , Cuchel Marina 
Published: October 2022

Purpose of review
We reviewed current and future therapeutic options for patients with homozygous familial hypercholesterolemia (HoFH) and place this evidence in context of an adaptable treatment algorithm.

Recent findings
Lowering LDL-C levels to normal in patients with HoFH is challenging, but a combination of multiple lipid-lowering therapies (LLT) is key. Patients with (near) absence of LDL receptor expression are most severely affected and frequently require regular lipoprotein apheresis on top of combined pharmacologic LLT. Therapies acting independently of the LDL receptor pathway, such as lomitapide and evinacumab, are considered game changers for many patients with HoFH, and may reduce the need for lipoprotein apheresis in future. Liver transplantation is to be considered a treatment option of last resort. Headway is being made in gene therapy strategies, either aiming to permanently replace or knock out key lipid-related genes, with first translational steps into humans being made. Cardiovascular disease risk management beyond LDL-C, such as residual Lp(a) or inflammatory risk, should be evaluated and addressed accordingly in HoFH.

Summary
Hypercholesterolemia is notoriously difficult to control in most patients with HoFH, but multi-LLT, including newer drugs, allows reduction of LDL-C to levels unimaginable until a few years ago. Cost and availability of these new therapies are important future challenges to be addressed.
Pancreatic Heterotopia in the Small Bowel
Authors: Chin Ning-Hsuan , Wu Jiann-Ming , Chen Kuan-Chih , Lee Tzong-Hsi , Lin Cheng-Kuan , Chung Chen-Shuan 
Published: October 2022

Abstract
Diagnosing pancreatic heterotopia (PH) is challenging, because it is a rare congenital anomaly. We report the case of a 66-year-old man who presented with ileus and jejunal PH diagnosed using single-balloon enteroscopy. Reviewing 178 cases of small intestinal PH in the literature showed that (1) PH mostly occurred at the duodenum (61.8%), followed by the jejunum (22.5%) and ileum (14.6%); (2) patients with ileal PH were younger (mean, 40.7 vs 54.6 years; P < 0.001), while those with jejunal PH were older (mean, 59.5 vs 51.7 years; P = 0.006); (3) most patients with jejunal PH were females, while those with duodenal or ileal PH were predominantly males (M:F = 0.8:1 vs 2.5:1; P = 0.003); (4) asymptomatic cases were rare (15.2% vs 83.4% in small and nonsmall bowel, respectively); (5) most patients with ileal PH presented with bleeding (61.5%), while the remaining had abdominal pain (42.8%); (6) emergent operation was performed in 11 cases (6.2%), mainly at the jejunum (12.5%) and Meckel’s diverticulum (25%); and (7) Heinrich’s classification may be inconclusive. Enteroscopy was performed in only 6 cases (3.4%), and earlier diagnosis and further minimally invasive procedures could have been achieved with enteroscopy.
Type 1 Diabetes in Acute Pancreatitis Consortium
Authors: Serrano Jose , Laughlin Maren R. , Bellin Melena D. , Yadav Dhiraj , Chinchilli Vernon M. , Andersen Dana K. ,   on behalf of the Type 1 Diabetes in Acute Pancreatitis Consortium (T1DAPC)
Published: October 2022

Abstract
Acute pancreatitis (AP), resulting from inflammation of the pancreas, accounts for more than 300,000 US hospital discharges per year. Although glucose intolerance has been known as a complication of severe AP, this effect was thought to be transient. Recently, cohort studies and meta-analysis of 24 published studies of 1100 patients who survived one or more episodes of AP revealed that 30% to 40% of patients developed diabetes or impaired glucose tolerance within 3 to 4 years of even a single episode of AP. The National Institute of Diabetes and Digestive and Kidney Diseases funded the Type 1 Diabetes in Acute Pancreatitis Consortium (T1DAPC) to undertake a prospective observational study of the occurrence of diabetes during an AP episode or subsequently, with emphasis on type 1 diabetes. Key factors for funding T1DAPC are the increasing incidence and prevalence of AP, its association with the development of type 1 diabetes and other forms of diabetes after AP, its complications, and associated health care cost. The T1DAPC structure, governance, and research objectives are described in this article. The DREAM (Diabetes RElated to Acute pancreatitis and its Mechanisms) studies to be undertaken by the T1DAPC are described in other articles in this journal's issue.
Rationale and Development of a Data Coordinating Center to Support the Type 1 Diabetes in Acute Pancreatitis Consortium
Authors: Dyer Anne-Marie , Baab Kendall Thomas , Merchlinski Aimee , Valencia-Moulton Paula A. , Holmes Beth R. , Pichardo-Lowden Ariana , Serrano Jose , Laughlin Maren R. , Chinchilli Vernon M. ,   on behalf of the Type 1 Diabetes in Acute Pancreatitis Consortium (T1DAPC)
Published: October 2022

Abstract
A data coordinating center (DCC) is a critical member of any multicenter research undertaking, and that is especially true for the Type 1 Diabetes in Acute Pancreatitis Consortium (T1DAPC). We describe how the T1DAPC DCC supports the consortium via its experience and expertise in project management, administration, financial management, regulatory compliance, scientific coordination, data management, research computing, and biostatistics and in facilitating scientific publications. The DCC's matrix management system has been extremely effective in managing all of its responsibilities. The first 16 months in the life of the T1DAPC have been dedicated to the development of its first protocol, titled Diabetes RElated to Acute pancreatitis and its Mechanisms (DREAM), addressing the institutional review board and regulatory components, developing the T1DAPC data management system, and providing training and certification of clinical center staff. As a result of its efforts, the DCC was a major contributor to the T1DAPC being able to initiate recruitment for the DREAM study in January 2022.
Empirical antibiotic therapy for difficult-to-treat Gram-negative infections: when, how, and how long?
Authors: Bassetti Matteo , Vena Antonio , Labate Laura , Giacobbe Daniele R. 
Published: October 2022

Purpose of review
To discuss empirical therapy for severe infections due to Gram-negative bacteria with difficult-to-treat resistance (GNB-DTR) in current clinical practice, focusing in particular on the positioning of novel therapeutic agents and rapid diagnostic tests.

Recent findings
The current era of novel agents active against GNB-DTR and showing differential activity against specific determinants of resistance is an unprecedented scenario, in which the clinical reasoning leading to the choice of the empirical therapy for treating severe GNB-DTR infections is becoming more complex, but it also allows for enhanced treatment precision.

Summary
Novel agents should be used in line with antimicrobial stewardship principles, aimed at reducing selective pressure for antimicrobial resistance. However, this does not mean that they should not be used. Indeed, excesses in restrictive uses may be unethical by precluding access to the most effective and less toxic treatments for patients with severe GNB-DTR infections. Given these premises (the ‘how’), empirical treatment with novel agents should be considered in all patients with risk factors for GNB-DTR and severe clinical presentation of acute infection (the ‘when’). Furthermore, empirical novel agents should preferably be continued only for a few hours, until de-escalation, modification, or confirmation (as targeted therapy) is made possible by the results of rapid diagnostic tests (the ‘how long’).
Welcome to the big leaves: best practices for improving genome annotation in non-model plant genomes
Authors: Vuruputoor Vidya S , Monyak Daniel , Fetter Karl C. , Webster Cynthia , Bhattarai Akriti , Shrestha Bikash , Zaman Sumaira , Bennett Jeremy , McEvoy Susan L. , Caballero Madison , Wegrzyn Jill L. 
Published: October 2022

ABSTRACT•Premise of the studyRobust standards to evaluate quality and completeness are lacking for eukaryotic structural genome annotation. Genome annotation software is developed with model organisms and does not typically include benchmarking to comprehensively evaluate the quality and accuracy of the final predictions. Plant genomes are particularly challenging with their large genome sizes, abundant transposable elements (TEs), and variable ploidies. This study investigates the impact of genome quality, complexity, sequence read input, and approach on protein-coding gene prediction.•MethodsThe impact of repeat masking, long-read, and short-read inputs,de novo, and genome-guided protein evidence was examined in the context of the popular BRAKER and MAKER workflows for five plant genomes. Annotations were benchmarked for structural traits and sequence similarity.•ResultsBenchmarks that reflect gene structures, reciprocal similarity search alignments, and mono-exonic/multi-exonic gene counts provide a more complete view of annotation accuracy. Transcripts derived from RNA-read alignments alone are not sufficient for genome annotation. Gene prediction workflows that combine evidence-based andab initioapproaches are recommended, and a combination of short and long-reads can improve genome annotation. Adding protein evidence fromde novo assemblies, genome-guided transcriptome assemblies, or full-length proteins from OrthoDB generates more putative false positives as implemented in the current workflows. Post-processing with functional and structural filters is highly recommended.•DiscussionWhile annotation of non-model plant genomes remains complex, this study provides recommendations for inputs and methodological approaches. We discuss a set of best practices to generate an optimal plant genome annotation, and present a more robust set of metrics to evaluate the resulting predictions.