bluuebunny/crossref_metadata_2025 huggingface dataset:
Mesenchymal Stem Cell-derived Extracellular Vesicles Prevent Experimental Bronchopulmonary Dysplasia Complicated By Pulmonary Hypertension
Authors: Sharma Mayank , Bellio Michael A , Benny Merline , Kulandavelu Shathiyah , Chen Pingping , Janjindamai Chawisa , Han Chenxu , Chang Liming , Sterling Shanique , Williams Kevin , Damianos Andreas , Batlahally Sunil , Kelly Kaitlyn , Aguilar-Caballero Daniela , Zambrano Ronald , Chen Shaoyi , Huang Jian , Wu Shu , Hare Joshua M , Schmidt Augusto , Khan Aisha , Young Karen
Published: June 2022

Mesenchymal stem cell (MSC) extracellular vesicles (EVs) have beneficial effects in preclinical bronchopulmonary dysplasia and pulmonary hypertension (BPD-PH) models. The optimal source, dosing, route, and duration of effects are however unknown. The objectives of this study were to (a) compare the efficacy of GMP-grade EVs obtained from Wharton’s Jelly MSCs (WJ-MSCs) and bone marrow (BM-MSCs), (b) determine the optimal dosing and route of administration, (c) evaluate its long-term effects, and (d) determine how MSC EVs alter the lung transcriptome. Newborn rats exposed to normoxia or hyperoxia (85% O2) from postnatal day (P)1-P14 were given (a) intra-tracheal (IT) BM or WJ-MSC EVs or placebo, (b) varying doses of IT WJ-MSC EVs, or (c) IT or intravenous (IV) WJ-MSC EVs on P3. Rats were evaluated at P14 or 3 months. Early administration of IT BM-MSC or WJ-MSC EVs had similar beneficial effects on lung structure and PH in hyperoxia-exposed rats. WJ-MSC EVs however had superior effects on cardiac remodeling. Low, medium, and high dose WJ-MSC EVs had similar cardiopulmonary regenerative effects. IT and IV WJ-MSC EVs similarly improved vascular density and reduced PH in hyperoxic rats. Gene-set enrichment analysis of transcripts differentially expressed in WJ-MSC EV-treated rats showed that induced transcripts were associated with angiogenesis. Long-term studies demonstrated that a single early MSC EV dose has pulmonary vascular protective effects 3 months after administration. Together, our findings have significant translational implications as it provides critical insight into the optimal source, dosing, route, mechanisms of action, and duration of effects of MSC-EVs for BPD-PH.
Inhibition of Canonical Wnt Signaling Promotes Ex Vivo Maintenance and Proliferation of Hematopoietic Stem Cells in Zebrafish
Authors: Kimura Koki , Yamamori Shiori , Hazawa Masaharu , Kobayashi-Sun Jingjing , Kondo Mao , Wong Richard W , Kobayashi Isao
Published: June 2022

The maintenance and proliferation of hematopoietic stem cells (HSCs) are tightly regulated by their niches in the bone marrow. The analysis of niche cells or stromal cell lines that can support HSCs has facilitated the finding of novel supporting factors for HSCs. Despite large efforts in the murine bone marrow; however, HSC expansion is still difficult ex vivo, highlighting the need for new approaches to elucidate the molecular elements that regulate HSCs. The zebrafish provides a unique model to study hematopoietic niches as HSCs are maintained in the kidney, allowing for a parallel view of hematopoietic niches over evolution. Here, using a stromal cell line from the zebrafish kidney, zebrafish kidney stromal (ZKS), we uncover that an inhibitor of canonical Wnt signaling, IWR-1-endo, is a potent regulator of HSCs. Coculture assays revealed that ZKS cells were in part supportive of maintenance, but not expansion, of gata2a:GFP+runx1:mCherry+ (gata2a+runx1+) HSCs. Transcriptome analysis revealed that, compared with candidate niche cells in the kidney, ZKS cells weakly expressed HSC maintenance factor genes, thpo and cxcl12, but highly expressed canonical Wnt ligand genes, wnt1, 7bb, and 9a. Thpo supplementation in ZKS culture slightly increased, but inhibition of canonical Wnt signaling by IWR-1-endo treatment largely increased the number of gata2a+runx1+ cells (>2-fold). Moreover, we found that gata2a+runx1+ cells can be maintained by supplementing both IWR-1-endo and Thpo without stromal cells. Collectively, our data provide evidence that IWR-1-endo can be used as a novel supporting factor for HSCs.
Foxp1 and Foxp4 Deletion Causes the Loss of Follicle Stem Cell Niche and Cyclic Hair Shedding by Inducing Inner Bulge Cell Apoptosis
Authors: Yang Qingchun , Zhang Jie , Bao Qianyi , Zhong Jialin , Wang Xiaoqing , Tao Yixin , Xu Xuegang , Lv Kaiyang , Wang Yushu , Li Baojie , He Lin , Guo Xizhi , Ma Gang
Published: June 2022

Quiescent hair follicle stem cells (HFSCs) reside in specialized bulge niche where they undergo activation and differentiation upon sensing niche-dependent signals during hair follicle (HF) homeostasis and wound repair. The underlying mechanism of HFSCs and bulge niche maintenance is poorly understood. Our previous study has reported that a transcription factor, forkhead box P1 (Foxp1), functions to maintain the quiescence of HFSCs. Here, we further discovered that forkhead box P4 (Foxp4), a close family member of Foxp1, had similar expression profiles in various components of HFs and formed a complex with Foxp1 in vitro and in vivo. The HF-specific deficiency of Foxp4 resulted in the precocious activation of HFSCs during hair cycles. In contrast to single Foxp1 or Foxp4 conditional knockout (cKO) mice, Foxp1/4 double cKO exerted an additive effect in the spectrum and severity of phenotypes in HFSC activation, hair cycling acceleration and hair loss, coupled with remarkable downregulation of fibroblast growth factor 18 (Fgf18) and bone morphogenetic protein 6 (Bmp6) expression in bulge cells. In addition, the double KO of Foxp1/4 induced the apoptosis of K6-positive (K6+) inner bulge cells, a well-established stem cell (SC) niche, thus resulting in the destruction of the bulge SC niche and recurrent hair loss. Our investigation reveals the synergistic role of Foxp1/4 in sustaining K6+ niche cells for the quiescence of HFSCs.
Brain functional topology differs by sex in cognitively normal older adults
Authors: Yang Zhengshi , Cieri Filippo , Kinney Jefferson W , Cummings Jeffrey L , Cordes Dietmar , Caldwell Jessica Z K ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: June 2022

Introduction

Late onset Alzheimer’s disease (AD) is the most common form of dementia, in which almost 70% of patients are women.

Hypothesis

We hypothesized that women show worse global FC metrics compared to men, and further hypothesized a sex-specific positive correlation between FC metrics and cognitive scores in women.

Methods

We studied cognitively healthy individuals from the Alzheimer’s Disease Neuroimaging Initiative cohort, with resting-state functional Magnetic Resonance Imaging. Metrics derived from graph theoretical analysis and functional connectomics were used to assess the global/regional sex differences in terms of functional integration and segregation, considering the amyloid status and the contributions of APOE E4. Linear mixed effect models with covariates (education, handedness, presence of apolipoprotein [APOE] E4 and intra-subject effect) were utilized to evaluate sex differences. The associations of verbal learning and memory abilities with topological network properties were assessed.

Result

Women had a significantly lower magnitude of the global and regional functional network metrics compared to men. Exploratory association analysis showed that higher global clustering coefficient was associated with lower percent forgetting in women and worse cognitive scores in men.

Conclusion

Women overall show lower magnitude on measures of resting state functional network topology and connectivity. This factor can play a role in their different vulnerability to AD.

Significance statement

Two thirds of AD patients are women but the reasons for these sex difference are not well understood. When this late onset form dementia arises is too late to understand the potential causes of this sex disparities. Studies on cognitively healthy elderly population are a fundamental approach to explore in depth this different vulnerability to the most common form of dementia, currently affecting 6.2 million Americans aged 65 and older are, which means that >1 in 9 people (11.3%) 65 and older are affected by AD. Approaches such as resting-state functional network topology and connectivity may play a key role in understanding and elucidate sex-dependent differences relevant to late-onset dementia syndromes.
Screening adults with tuberculosis for severe illness at notification: programme experience from Gujarat, India
Authors: Patel Bharatkumar Hargovandas , Shewade Hemant Deepak , Davara Kajal Bhagavanjibhai , Mehta Kedar Gautambhai , Modi Bhavesh Vitthalbhai , Vyas Monark Jitendrabhai , Murthy Hosadurga Jagadish Deepak , Vanitha Basavarajachar , Kumar Ajay M V
Published: June 2022

Background

National tuberculosis (TB) programmes in high-burden countries do not systematically assess severity at diagnosis followed by referral for inpatient care. Due to limited capacity, comprehensive assessment of all TB patients is not practical. In three districts of Gujarat (West India) in June 2021, we determined the feasibility of screening for severe illness by paramedical staff of public facilities and the burden of ‘high risk for severe illness’ at notification among adults (≥15 y of age) with TB.

Methods

In this cross-sectional study, the screening criteria for high risk for severe illness was the presence of any one of the following: body mass index (BMI) ≤14.0 kg/m2, BMI ≤16.0 kg/m2 with bilateral leg swelling, respiratory rate >24/min, oxygen saturation <94% or inability to stand without support. We summarized the feasibility indicators and burden using proportion (95% confidence interval [CI]) and median, as applicable.

Results

Of 626 notified adults, 87% were screened. The median time interval for screening was 3 d from notification and all indicators were collected in 97% of patients. The burden of high risk for severe illness was high, at 41.6% (95% CI 37.5 to 45.8).

Conclusions

High burden and feasibility (high coverage, acceptable time interval and minimal missing data) makes a strong case for routine screening of severe illness.
Re-evaluation of the Fungal Diversity and Pathogenicity of Cytospora Species from Populus in China
Authors: Lin Lu , Pan Meng , Bezerra Jadson D. P. , Tian Chengming , Fan Xinlei
Published: June 2022

Poplar is widely cultivated in China because of its strong ecological adaptability, fast growth, easy reproduction, and short rotation period. However, it suffers from severe threat from canker disease caused by Cytospora species. The present study revealed the presence of Cytospora species from Populus in China. A total of six species of Cytospora were isolated from Populus in six provinces in China, including five known species (C. ailanthicola, C. chrysosperma, C. donglingensis, C. paratranslucens, and C. sophoriopsis) and one novel species (C. populi) based on morphological and phylogenetic analyses of ITS, act, rpb2, tef1-α, and tub2 gene sequences. Cytospora ailanthicola, C. chrysosperma, C. paratranslucens, and C. sophoriopsis are confirmed as pathogens by pathogenicity tests of which C. paratranslucens showed the strongest virulence, followed by C. ailanthicola, C. chrysosperma, and C. sophoriopsis. The mycelial growth rates of isolates from the six species had 22.5 to 27°C as the optimum temperatures, and the optimum pH values were 5.9 to 7.1. The effectiveness of six carbon sources on the mycelial growth showed that colonies grew the fastest in the presence of fructose and grew the slowest using xylose. This study represents a significant evaluation of Cytospora causing poplar canker disease in China.
“What are my options?”
Authors: Bartholomew Melissa Boettger
Published: June 2022

Patients may choose to have a conversation with their providers about their care options. This article presents a guide for NPs for these goals-of-care conversations. NPs having these conversations can follow the strategies presented to plan the discussion, overcome barriers, and offer useful resources and support.
Intrarenal pseudoaneurysm after percutaneous nephrolithotomy: a case report
Authors: Moussa Mohamad , Chakra Mohamad Abou , Dellis Athanasios , Papatsoris Athanasios G.
Published: June 2022

Background:

Percutaneous nephrolithotomy (PNL) is the gold standard to treat large or complex renal stones. Intrarenal pseudoaneurysm is a rare, yet clinically significant, complication of PNL.

Case summary:

A 58-year-old man with a 3 cm calculus in the lower calyx of the left kidney was operated on by PNL 3 days before presentation to the emergency department. The patient presented with massive hematuria and dizziness. Upon presentation, the patient appeared uncomfortable and in distress. He was in hemorrhagic shock. The patient was resuscitated with intravenous fluids and blood transfusion. An urgent computed tomography scan showed multiple clots in the left renal pelvis and bladder with a retroperitoneal hematoma. The patient underwent angiography which revealed an inferior pole branch pseudoaneurysm. The pseudoaneurysm was treated by endovascular embolization with N-butyl-2-cyanoacrylate. No postoperative complications were seen.

Conclusion:

Selective renal artery embolization is an effective treatment for pseudoaneurysm post PNL with excellent outcomes.
Varied presentations, magnitude, and outcome of traumatic neck injuries at a level I trauma center
Authors: Dar Parvez Mohi Ud Din , Boddeda Jogendra , Kaur Supreet , Priyadarshini Pratyusha , Kumar Abhinav , Bagaria Dinesh , Choudhary Narendra , Alam Junaid , Sagar Sushma , Kumar Subodh , Gupta Amit , Mishra Biplab
Published: June 2022

Introduction:

Traumatic neck injuries (TNIs) constitute 5%–10% of all trauma cases. These injuries can be caused by either penetrating or blunt trauma. Patients can have a varied presentation like cut injury over the neck, bleeding, neck swelling, breathing difficulty, dysphagia, etc.

Methods:

This was a retrospective observational study conducted at a level I trauma center in India from January 2016 to March 2020. One hundred thirty patients who required admission and intervention due to TNIs were included in this study.

Results:

One hundred thirty patients with neck injuries were included in this study. Males were predominant (91.5%) with the age ranging from 10 to 70 years. The most common mechanism of injury was physical assault (40.7%), followed by road traffic injury (23.8%) and self-inflicted injuries (18.4%). Penetrating trauma was predominant. Open neck wound with bleeding was the most common presenting symptom. Zone II injuries were more common (83.8%) followed by zone I (12.3%) and zone III (3.8%). Soft tissue injury including skin, platysma breach, and strap muscle injury was present in 46.9% of patients. Laryngopharyngeal injury was present in 13.8%, tracheal injury in 28.5%, vascular injury in 13.8%, and esophageal injury in 4.6% of patients.

Conclusion:

Penetrating neck trauma is more common than blunt in developing countries like India. Advanced Trauma Life Support (ATLS) protocol guides the initial management. The definitive management depends on the type and mechanism of injury, anatomical level, severity, and the organ injured.
Renaming NAFLD to MAFLD: Advantages and Potential Changes in Diagnosis, Pathophysiology, Treatment, and Management
Authors: Rui Fajuan , Yang Hongli , Hu Xinyu , Xue Qi , Xu Yayun , Shi Junping , Li Jie
Published: June 2022

In recent years, with the increasing incidence of obesity and other metabolic diseases, the prevalence of non-alcoholic fatty liver disease (NAFLD) has increased and it has become a major health problem affecting more than one quarter of the world's population. Recently, experts reached a consensus that NAFLD does not reflect the current knowledge, and metabolic dysfunction-associated fatty liver disease (MAFLD) was suggested as a more appropriate term. MAFLD is not just a simple renaming of NAFLD. The definition of MAFLD allows a patient to have dual (or more) etiologies for their liver disease, which will help to exclude more heterogeneous patients. In this review, we introduce the significant differences between the definitions of NAFLD and MAFLD. In addition, we also describe the advantages of the term MAFLD in the pathophysiology, therapy, and patient management.
Assessing the risk for falls among Portuguese community-dwelling stroke survivors. Are we using the better tools? Observational study
Authors: Pimenta Carla , Correia Anabela , Alves Marta , Virella Daniel
Published: June 2022

Purpose:

This study assesses the estimation of the risk for falls among community-dwelling stroke survivors referred for ambulatory physiotherapy and explores factors that affect the risk.

Methods:

Observational, cross-sectional with nested case-control study, of individuals, referred to physiotherapy less than 12 months after stroke and able to walk independently. Berg Balance Scale, Timed Up and Go Test, and the Motor Assessment Scale were applied. Berg Balance Scale ≤45 or Timed Up and Go Test > 14 were used to estimate the risk for falls. The discrimination ability of the estimation was assessed. Alternative models were explored by logistic regression analysis.

Results:

One hundred sixty-seven patients fulfilled the inclusion criteria. Patients were 21 to 87years old (median 66), 98 men (58.7%), and in 133 (79.6%) the stroke occurred in the last 6 months. Falls were reported by 78 (46.7%) of the patients but 139 (83.2% [95%CI 76.84–88.14]) were estimated as having risk for falls. The discrimination ability of the estimation of the actual occurrence of falls by Berg Balance Scale ≤45 or Timed Up and Go Test >14 was 55% (95%CI 47.5–62.4). The actual occurrence of falls was associated only with Motor Assessment Scale, as a protective factor. The discrimination ability of the estimation of the actual occurrence of falls by Motor Assessment Scale alone was area under the curve 0.69 (95%CI 0.60–0.77).

Conclusions:

Different tools with better performance are needed to identify the risk for falls after stroke.
SARS-CoV-2 seroprevalence in healthcare workers: The experience of a Portuguese COVID-19 front-line hospital during the 1st pandemic wave
Authors: Ramos Angelica , Araújo Beatriz , Lacerda Lisa , Flora Ana Lúcia , Ribeiro Luis , Patrício Emília , Cardoso Maria João , Guimarães João Tiago
Published: June 2022

Background:

Healthcare workers (HCW) are at increased risk of SARS-CoV-2 infection. Here, we describe the SARS-CoV-2 seroprevalence in HCW who work daily at a COVID-19 front-line hospital in Portugal.

Methods:

To this end, the seroprevalence of 1027 HCW, assessed after the peak of the first pandemic wave, was determined using the following immunoassays: Euroimmun Anti-SARS-CoV-2 ELISA IgG (Euroimmun, Luebeck, Germany), Abbott SARS-CoV-2 IgG (Abbott Laboratories, Chicago), and Elecsys Anti-SARS-CoV–2 Total (Roche Diagnostics, Basel, Switzerland).

Results:

We found a 2.7% seroprevalence, very close to the one determined in the community (2.9%) for the same period.

Conclusions:

This low SARS-CoV–2 seroprevalence highlights the effectiveness of infection prevention and control measures implemented very early in the pandemic, namely the use of appropriate personal protective equipment.
Cost-Effectiveness Analysis: Personal Systems Approach in Improving Medication Adherence in Adult Kidney Transplant Patients
Authors: Whittington Melanie , Goggin Kathy , Noel-MacDonnell Janelle , Hathaway Donna , Remy Laura , Aholt Dana , Clark Debra , Miller Courtney , Ashbaugh Catherine , Wakefield Mark , Ellis Rebecca B. , Russell Cynthia
Published: June 2022

Interventions to improve medication nonadherence in transplantation have recently moved from a focus on motivation and intention, to a focus on person-level quality improvement strategies. These strategies link adherence to established daily routines, environmental cues, and supportive people. The objective of this evaluation was to estimate the cost of implementation and the cost-effectiveness of a person-level intervention shown to increase medication adherence. To estimate the intervention costs, a direct measure microcosting approach was used after key informant interviews with project champions and a review of implementation expenditures. Cost-effectiveness was calculated by comparing the incremental implementation costs and healthcare costs associated with nonadherence to the incremental percent adherent, defined as the percent of patients who took greater or equal to 85% of their medication doses, for each pairwise comparison. The intervention was low-resource to implement, costing approximately $520 to implement per patient, and was associated with significant improvements in medication adherence. These implementation costs were more than outweighed by the expected healthcare savings associated with improvements in adherence. This person-level intervention is a low-cost, efficacious intervention associated with significant statistical and clinical improvements in medication adherence in adult kidney transplant recipients.
Arthroscopic Treatment for Femoroacetabular Impingement Syndrome in Adolescents: A Systematic Review and Meta-Analysis
Authors: Huang Hong-jie , Zhou Xiang , Huang Zhi-gao , Dang Han-han , Xue Shi-lin , Zhang Zhi-yu , Zhang Xin , Wang Jian-quan
Published: June 2022

Objective:

The objective of this review was to analyze the effect of arthroscopic surgery for femoroacetabular impingement syndrome (FAI) in adolescents and factors that may influence the revision rate.

Design:

Systematic review and meta-analysis.

Setting:

PubMed, Scopus, Cochrane Library, EMBASE, and MEDLINE were searched from their earliest records to May 2021.

Patients:

Adolescents who underwent primary arthroscopic treatment for FAI.

Interventions:

Hip arthroscopic treatment.

Main Outcome Measures:

Patient-reported outcomes (PROs), alpha angle, revision rates, and the rate of complications.

Results:

A total of 832 hips in 753 patients were included in this study. All PROs improved significantly. The modified Harris Hip Score pooled mean difference was 24.99 (95% CI, 22.88-27.10, P < 0.0001, I2 = 19.9%), Hip Outcome Score (HOS)–Sports-Specific Subscale was 35.88 (95% CI, 33.07-38.68, P < 0.0001, I2 = 0%), HOS–Activities of Daily Living was 23.53 (95% CI, 21.21-25.85, P < 0.0001, I2 = 0%), and the Nonarthritic Hip Score was 22.34 (95% CI, 18.40-26.28, P < 0.0001, I2 = 40.9%). The visual analog scale for pain decreased by 40.39 (44.39-36.40, P < 0.0001, I2 = 0%). The alpha angle decreased by 22.0 degrees from 62.9 degrees to 40.9 degrees after arthroscopic surgery. The rate of complication and revision surgery was 1.2% (10/832) and 3.4% (28/832), respectively, with high postoperative patient satisfaction.

Conclusions:

All PROs significantly improved after surgery, with a low rate of complications and reoperation. High postoperative patient satisfaction was also reported.
Outcomes in cardiogenic shock: the role of surrogate endpoints
Authors: Kosyakovsky Leah B. , Marbach Jeffrey A. , Nguyen Khoa , Mukundan Srini , Chweich Haval , Kapur Navin K.
Published: June 2022

Purpose of review

Early revascularization, invasive hemodynamic profiling, and initiation of temporary mechanical circulatory support (MCS) have all become routine components of cardiogenic shock (CS) management. Despite this evolution in clinical practice, patient selection and timing of treatment initiation remain a significant barrier to achieving sustained improvement in CS outcomes. Recent efforts to standardize CS management, through the development of treatment algorithms, have relied heavily on surrogate endpoints to drive therapeutic decisions. The present review aims to provide an overview of the basis of evidence for those surrogate endpoints commonly employed in clinical trials and CS management algorithms.

Recent findings

Recent publications from both observational and randomized cohorts have demonstrated the utility of surrogate endpoints in risk stratifying patients with CS. In particular, invasive hemodynamics using pulmonary artery catheters to guide initiation and weaning of MCS, biochemical markers that portend imminent end-organ failure, and clinical risk scores that combine multiple hemodynamic and laboratory parameters have demonstrated an ability to prognosticate outcomes in patients with CS.

Although further validation is necessary, multiple clinical, hemodynamic, and biochemical markers have demonstrated utility as surrogate endpoints in CS, and will undoubtedly assist physicians in clinical decision-making.
Inhaled opioids for cancer pain relief
Authors: Osowicka Magdalena , Janowiak Piotr , Gorzewska Agnieszka , Lichodziejewska-Niemierko Monika
Published: June 2022

Despite the many new possibilities, cancer pain treatment is not always effective and often poses a challenge for practitioners. At the end-of-life care, both oral and subcutaneous drug delivery very often are not attainable. The increasing number of patients in terminal stage of chronic diseases forced us to look for the alternative ways of administration of pain treatment. In this context, the potentially rapid onset of action and ease of use make aerosolized drug delivery an attractive option in palliative care settings. The objective of this review was to identify literature on pain relief with inhaled opioids. The evidence suggests that nebulized opioids might be effective in the treatment of pain in various aetiologies; however, randomized controlled studies on nebulization therapy for cancer pain are lacking.
Impact of shift work on irritable bowel syndrome and functional dyspepsia
Authors: Wang Nian , Liu Xinghuang , Ye Weixiang , Shi Zhaohong , Bai Tao
Published: June 2022

Background:

The possible association between shift work with irritable bowel syndrome (IBS) and functional dyspepsia (FD) remains controversial. The purpose of the study is to conduct a meta-analysis to explore the potential association between shift work with IBS/FD.

Methods:

We searched relevant observational studies on Medline (PubMed) and Embase until June 30, 2021. Two different investigators extracted data and assessed the quality of each study independently. The meta-analysis was used to evaluate the pooled odds risk (OR) between shift work and IBS/FD.

Results:

Eight studies were included ultimately. Shift workers were more likely to suffer from IBS. The OR of shift work was 1.81 (95% confidence interval 1.42; 2.32) with low heterogeneity (P < .05, I
2 = 0%) for IBS. However, no evidence of the association was observed between shift work and the risk of FD. The OR of shift work was 0.87 (95% confidence interval 0.62; 1.23) (P > .05) for FD.

Conclusions:

There was a positive association between shift work and IBS. The prevalence of IBS was 81% higher among shift workers than among non-shift workers. Shift work was probably a risk factor for IBS. The low heterogeneity supports the reliability of the results. However, there was no significant association between shift work and FD. The strength of the evidence was limited and further prospective cohort studies were needed.
Risk of developing cognitive impairment on patients with chronic obstructive pulmonary disease
Authors: Simargi Yopi , Mansyur Muchtaruddin , Turana Yuda , Harahap Alida R. , Ramli Yetty , Siste Kristiana , Prasetyo Marcel , Rumende Cleopas Martin
Published: June 2022

Background:

The increasing number of chronic obstructive pulmonary disease (COPD) incidence has led to a great negative impact on older people's lives. This chronic disease was a critical and independent risk factor for cognitive function impairment in the elderly with mild cognitive impairment as a frequent feature. This systematic review aimed to examine the risk of developing cognitive impairment in COPD.

Methods:

A structured search of the literature was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement guideline, with a pre-determined search strategy starting from study identification, title and abstract screening, eligibility assessment, and inclusion of relevant study. The search was conducted in PubMed and MEDLINE via EBSCOhost, with restriction to human studies. The studies from inception until January 12, 2021.

Results:

Five original articles were included. Most studies found that patients with COPD had a higher chance of developing cognitive impairment, especially when patients were followed up for more than 5 years. We discovered that the risk of cognitive impairment seemed to be correlated with the length of time spent following the participants, with the highest risk of cognitive impairment being identified in those who had the longest observation period. It is critical to conduct cognitive screening from the time a diagnosis of COPD is obtained and on a continuing basis in order to recognize and treat these individuals appropriately.

Conclusion:

There is a potential association between COPD and mild cognitive impairment. We encourage more studies to be done with higher sensitivity and specificity cognitive screening tools in the future to build better evidence and qualify to be analyzed quantitatively with meta-analysis.
One-year efficacy of tenofovir alafenamide in patients with chronic hepatitis B
Authors: Chen Yi-Cheng , Hsu Chao-Wei , Chien Rong-Nan , Tai Dar-In
Published: June 2022

Non-inferior antiviral efficacy and better renal safety have been reported in chronic hepatitis B patients with tenofovir alafenamide (TAF) treatment. The experience in real-world clinical practice is limited.

We aimed to explore the efficacy after 1-year TAF treatment.

A total of 148 patients (42 HBeAg-positive and 106 HBeAg-negative) with TAF treatment ≥1 year were included. Virological suppression (<20 IU/mL or undetectable), HBsAg level, alanine aminotransferase (ALT) normalization (≤36 U/L), and estimated glomerular filtration rate (eGFR) were analyzed at 1 year. Multivariate logistic regression analysis was performed to determine the associated factors for virological suppression and ALT normalization.

Virological suppression was achieved in 83% and the 1-year median decline of hepatitis B virus DNA was 5.18 log IU/mL. ALT normalization occurred in 75.7%. HBsAg level decreased at a median of 0.27 log IU/mL with significant difference from baseline (P < .001). Baseline ALT (odds ratio [OR] 1.005, 95% confidence interval [CI] 1.000–1.010, P = .036) and hepatitis B virus DNA (OR 0.222, 95% CI 0.079–0.621, P = .004) were significant factors for 1-year virological suppression. Age (OR 1.064, 95% CI 1.003–1.130, P = .041) was associated with ALT normalization. Significant changes were observed in creatinine (mean increase 0.03 mg/dL, P = .011) and eGFR (mean decrease 2.6 mL/min/1.73 m2, P = .004) after 1-year TAF treatment.

One-year TAF treatment came to good virological response, modest ALT normalization rate and significant HBsAg decline. The observation of significant changes in eGFR warranted further studies.
Recurrent spinal cord compression due to extramedullary hematopoiesis in thalassemia patient
Authors: Abbarh Shahem , Al-Mashdali Abdulrahman F. , Abdelrazek Mohamed , Gurusamy Venkada Manickam , Yassin Mohamed A.
Published: June 2022

Introduction:

Spinal cord compression secondary to extramedullary hematopoiesis (EMH) is a rare condition. Variable treatment options have been reported with different efficacy and recurrence rate. Due to its rarity, no clear optimal management guidelines have been established yet.

Patient concerns and diagnosis:

We report a recurrence of spinal cord compression secondary to EMH in a 19-year-old male, with a background of transfusion-dependent beta-thalassemia on luspatercept, who presented with weakness in both lower limbs.

Interventions and outcomes:

He was treated successfully both times with radiotherapy.

Conclusion:

Early diagnosis and management of EMH compressing the spinal cord are essential to prevent permanent neurological damage. Diagnosis should be suspected based on the clinical presentation and magnetic resonance imaging findings in a patient with a history of ineffective hemopoiesis. Treatment option remains controversial. Radiotherapy option seems effective, even in recurrent cases, and valid, particularly for those at high risk of surgery or who do not prefer it.
Exploring the relationship between osteoporosis and polycystic ovary syndrome based on bioinformatics
Authors: Dang Chun-xiao , Wang Ding , Yu Xiao , Liu Peng-fei , Liu Jin-xing
Published: June 2022

Background:

In recent years, clinical studies have found that there is a close relationship between osteoporosis and polycystic ovary syndrome. However, there are few literature on the pathogenesis of osteoporosis and polycystic ovary syndrome. In order to clarify their common pathogenic mechanism and provide potential targets for drugs to regulate them at the same time, bioinformatics methods are used to explore, so as to provide a new direction for the study of the relationship between diseases in the future.

Methods:

To screen the targets of osteoporosis and polycystic ovary syndrome by Genecards, Online Mendelian Inheritance in Man databases and Therapeutic Target Database to take the intersection of the two mappings and upload the intersection targets to the STRING database to construct protein-protein interaction network; to screen the core targets by degree value and import them to Metascape database for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis; and finally, to construct the visualization network of core targets and pathways by Cytoscape software. Ethical approval and informed consent of patients are not required because the data used in this study is publicly available and does not involve individual patient data or privacy.

Results:

The core targets of polycystic ovary syndrome and osteoporosis were insulin gene, insulin-like growth factor 1, CTNNB1, serine/threonine kinase 1, signal transducer and activator of transcription 3, LEP, etc. The biological processes involved include the regulation of protein phosphorylation, cell proliferation and differentiation, hormone endocrine, reproductive system and skeletal system. The related pathways were concentrated in Foxo signaling pathway, HTLV-I infection, PI3K-AKT signaling pathway, MAPK signaling pathway and AGE-RAGE signaling pathway in diabetic complications.

Conclusions:

There is a close relationship between osteoporosis and polycystic ovary syndrome in terms of target and molecular mechanism. This study used bioinformatics to clarify their targets and mechanisms, providing potential targets for drugs to regulate both diseases simultaneously and providing new directions to explore the relationship between the diseases.
Accuracy of the Hammersmith infant neurological examination for the early detection of neurological changes in infants exposed to Zika virus
Authors: de Souza Tathiana Ghisi , Bagne Eduardo , Mizani Renata , Rotob Ali Abdalla , Gazeta Rosa Estela , de Sene Amâncio Zara Ana Laura , Jundiaí Cohorte Zika virus , Passos Saulo Duarte
Published: June 2022

The Hammersmith infant neurological examination (HINE) is a highly predictive tool for the easy and low-cost detection of cerebral palsy. Between 2015 and 2016, the rapid spread of the Zika virus (ZIKV) in Brazil was responsible for an increase in microcephaly cases. This study aimed to verify the accuracy of the HINE for the early detection of neurological problems in Brazilian babies exposed to ZIKV.

This was a cross sectional case-control study of children exposed to ZIKV. This study was part of the Jundiaí ZIKV Cohort. Of a total sample of 782 children, 98 were evaluated (26 in the exposed group and 63 in the control group). We included late preterm infants and term infants who were exposed to the ZIKV and were participants in the ZIKV Cohort study. Student's t-test and stepwise multivariate logistic regression were used to compare groups.

Of the 26 items evaluated in the five scored categories of the HINE (cranial nerve function, posture, movements, tone, reflexes, and reactions), only the difference in ankle dorsiflexion between the exposed and the control groups was statistically significant. However, some items showed a significant trend in relation to the control group.

Our results demonstrated the importance of early neurological assessment of infants exposed to ZIKV, even in those without a microcephaly diagnosis.
Microneedling Outcomes in Early Post-Surgical Scars
Authors: Claytor R. Brannon , Sheck Casey G. , Chopra Vinod
Published: June 2022

Background:

Scars are a vexing sequela of surgery. Microneedling, also known as Minimally Invasive Percutaneous Collagen Induction (MIPCI), has demonstrated impressive improvements in chronic acne scars; however, no evidence exists for treating post-surgical scars during active wound healing. The purpose of this study was to demonstrate the utility and safe use of MIPCI in acute post-surgical scars.

Methods:

Twenty-five subjects who underwent surgery had scars treated with 3 treatments of MIPCI in the postoperative period. Scar assessment was measured by Vancouver Scar Scale (VSS), Patient & Observer Scar Assessment Scale (POSAS) and Global Aesthetic Improvement Scale (GAIS) after each of the 3 treatments and at final 2 month follow up.

Results:

Patients had positive improvement in VSS, POSAS and GAIS at 16-week post treatment initiation evaluation compared to initial measurement (p value<0.001). No statistically significant differences were noted when comparing the age of the patient, location of scars or Fitzpatrick Phototype Scales between patients. However, when comparing patients who began treatment early (week 6 to 7 post-op) to those who began treatment late (week 13 to 16 postop), there was a statistically significant difference in the POSAS group (p value <0.04).

Conclusions:

Post-surgical scars treated with MIPCI in the maturation and remodeling phase had no adverse outcomes. Interestingly, our data shows treatment initiated early in the maturation phase (6-7 weeks post-op) while natural collagen formation was tapering off demonstrated improved aesthetic outcomes compared to treatments initiated late in the maturation phase (13-16wk post-op).
Accurate Reconstruction of Mandibular Defects With Vascularized Bone Flaps Through Utilization of Mandible Space-Retention Guides
Authors: Wang Chengyi , Meng Zhaoqiang , Jie Bimeng , Li Ruiliu , He Yang , Xu Mingming
Published: June 2022

Purpose:

Comprehensive evaluation of the effects of using computer-aided design and space retention guide technology to reconstruct mandibular defects using vascularized autogenous bone flaps.

Method:

This study included 8 patients who received autogenous bone flaps (2 cases of vascularized fibula flaps and 6 cases of vascularized iliac flaps) for mandibular defect reconstruction at Peking University School and Hospital of Stomatology, from July 2018 to May 2021. All patients received digital surgery planning, computer aided design/computer aided manufacture, surgical guide technique for the removal of diseased bone segments, as well as vascularized fibular flap/iliac flap reconstruction. Three-dimensional deviations were analyzed after the operation.

Result:

The mandibular defects of all 8 patients were successfully reconstructed using the vascularized fibular flap/iliac bone flap. There were no serious complications at either the donor site or recipient site during our follow-up. The average three-dimensional deviation of all 8 patients was 1.92 mm, based on comparisons of preoperative design and actual postoperative computed tomography.

Conclusion:

Utilizing computer aided design/computer aided manufacture, we designed a new mandibular space-retention guide, which can accurately translate the preoperative digital design plan to real-time surgery with satisfactory accuracy and efficacy.
The Efficacy of Senna Bowel Preparation for Colonoscopy
Authors: Tian Hefeng , Fan Ying , Yang Lei , Hou Sai , Huang Wen , Dong Ruizhi , Li Shaodong , Zhu Xuanrui , Liu Wenlong , Shi Guanghuan , Li Xiaoke , Zhou Shiping , Wang Xiu
Published: June 2022

The quality of bowel preparation is an extremely important determinant of colonoscopy results. However, the efficacy of senna regimens in improving bowel cleanliness is uncertain. We conducted a systematic review and meta-analysis to synthesize data on whether using a senna bowel preparation regimen enhances the bowel cleanliness. We searched Web of Science Core Collection, MEDLINE, PubMed, Embase, Cochrane Library, and Scopus databases (from the inception to August 2021). The primary efficacy outcome was bowel cleanliness. Secondary outcomes included patient compliance, tolerance, and adverse events. Eleven trials fulfilled the inclusion criteria (3,343 patients. Overall, we found no significant differences in bowel cleanliness between the senna regimen and other bowel preparation regimens (odds ratio [95% confidence interval]: 1.02 [0.63, 1.67], p = 0.93). There was significant difference in tolerance (odds ratio [95% confidence interval]: 1.66 [1.08, 2.54], p = .02) and compliance (odds ratio [95% confidence interval]: 3.05 [1.42, 6.55], p = .004). The senna regimen yielded a significantly greater proportion of no nausea (odds ratio [95% confidence interval]: 1.84 [1.45, 2.32]) and vomiting (odds ratio [95% confidence interval]: 1.65 [0.81, 3.35]). Compared with other bowel preparation regimens, the senna regimen may be effective and safe in bowel cleaning before colonoscopy, with superior compliance and tolerance.
Pancreatic Cancer Patient-derived Organoids Can Predict Response to Neoadjuvant Chemotherapy
Authors: Demyan Lyudmyla , Habowski Amber N. , Plenker Dennis , King Daniel A. , Standring Oliver J. , Tsang Caitlin , St. Surin Luce , Rishi Arvind , Crawford James M. , Boyd Jeff , Pasha Shamsher A. , Patel Hardik , Galluzzo Zachary , Metz Christine , Gregersen Peter K. , Fox Sharon , Valente Cristina , Abadali Sonya , Matadial-Ragoo Steffi , DePeralta Danielle K. , Deutsch Gary B. , Herman Joseph M. , Talamini Mark A. , Tuveson David A. , Weiss Matthew J.
Published: June 2022

Objective:

To evaluate if patient-derived organoids (PDOs) may predict response to neoadjuvant (NAT) chemotherapy in patients with pancreatic adenocarcinoma.

Background:

PDOs have been explored as a biomarker of therapy response and for personalized therapeutics in patients with pancreatic cancer.

Methods:

During 2017–2021, patients were enrolled into an IRB-approved protocol and PDO cultures were established. PDOs of interest were analyzed through a translational pipeline incorporating molecular profiling and drug sensitivity testing.

Results:

One hundred thirty-six samples, including both surgical resections and fine needle aspiration/biopsy from 117 patients with pancreatic cancer were collected. This biobank included diversity in stage, sex, age, and race, with minority populations representing 1/3 of collected cases (16% Black, 9% Asian, 7% Hispanic/Latino). Among surgical specimens, PDO generation was successful in 71% (15 of 21) of patients who had received NAT prior to sample collection and in 76% (39 of 51) of patients who were untreated with chemotherapy or radiation at the time of collection. Pathological response to NAT correlated with PDO chemotherapy response, particularly oxaliplatin. We demonstrated the feasibility of a rapid PDO drug screen and generated data within 7 days of tissue resection.

Conclusion:

Herein we report a large single-institution organoid biobank, including ethnic minority samples. The ability to establish PDOs from chemotherapy-naive and post-NAT tissue enables longitudinal PDO generation to assess dynamic chemotherapy sensitivity profiling. PDOs can be rapidly screened and further development of rapid screening may aid in the initial stratification of patients to the most active NAT regimen.
Single molecule methylation profiles of cell-free DNA in cancer with nanopore sequencing
Authors: Lau Billy T. , Almeda Alison , Schauer Marie , McNamara Madeline , Bai Xiangqi , Meng Qingxi , Partha Mira , Grimes Susan M. , Lee HoJoon , Heestand Gregory M. , Ji Hanlee P.
Published: June 2022

Epigenetic characterization of cell-free DNA (cfDNA) is an emerging approach for characterizing diseases. We developed a strategy using nanopore-based single-molecule sequencing to measure cfDNA methylomes. This approach generated up to hundreds of millions of reads per cfDNA sample from cancer patients, an order of magnitude improvement over existing nanopore methods. Leveraging methylomes of matched tumors and immune cells, we characterized cfDNA methylomes of cancer patients for longitudinal monitoring during treatment.
Ticagrelor combined with aspirin displays the signature of regulating the gut microbiome in consistence with improving the immuno-inflammatory response in atherosclerosis
Authors: Bai Zhixia , Zhang Qinning , Liu Yajuan , Zhao Yang , Yan Ru , Yang Libo , Ma Huiyan , Ren Yi , Wang Ting , Li Yiwei , Liu Yuanyuan , Jiang Xin , Wang Rui , Jia Shaobin , Zhang Xiaoxia , Wang Hao
Published: June 2022

The authors have withdrawn their manuscript because the article needs to supplement the data of cell culture to clarify the mechanism. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Systems Analysis of de novo Mutations in Congenital Heart Diseases Identified a Molecular Network in Hypoplastic Left Heart Syndrome
Authors: Wang Yuejun Jessie , Zhang Xicheng , Lam Chi Keung , Guo Hongchao , Wang Cheng , Zhang Sai , Wu Joseph C. , Snyder Michael , Li Jingjing
Published: June 2022

Congenital heart diseases (CHD) are a class of birth defects affecting ∼1% of live births. These conditions are hallmarked by extreme genetic heterogeneity, and therefore, despite a strong genetic component, only a very handful of at-risk loci in CHD have been identified. We herein introduced systems analyses to uncover the hidden organization on biological networks of genomic mutations in CHD, and leveraged network analysis techniques to integrate the human interactome, large-scale patient exomes, the fetal heart spatial transcriptomes, and single-cell transcriptomes of clinical samples. We identified a highly connected network in CHD where most of the member proteins had previously uncharacterized functions in regulating fetal heart development. While genes on the network displayed strong enrichment for heart-specific functions, a sub-group, active specifically at early developmental stages, also regulates fetal brain development, thereby providing mechanistic insights into the clinical comorbidities between CHD and neurodevelopmental conditions. At a small scale, we experimentally verified previously uncharacterized cardiac functions of several novel proteins employing cellular assays and gene editing techniques. At a global scale, our study revealed developmental dynamics of the identified CHD network and observed the strongest enrichment for pathogenic mutations in the network specific to hypoplastic left heart syndrome (HLHS). Our single-cell transcriptome analysis further identified pervasive dysregulation of the network in cardiac endothelial cells and the conduction system in the HLHS left ventricle. Taken together, our systems analyses identified novel factors in CHD, revealed key molecular mechanisms in HLHS, and provides a generalizable framework readily applicable to studying many other complex diseases.