bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Clinical, Gram Stain, and Microbiological Cure Outcomes in Men Receiving Azithromycin for Acute Nongonococcal Urethritis: Discordant Cures Are Associated With Mycoplasma genitalium Infection
Authors: Toh Evelyn , Gao Xiang , Williams James A. , Batteiger Teresa A. , Coss Lisa A. , LaPradd Michelle , Ren Jie , Geisler William M. , Xing Yue , Dong Qunfeng , Nelson David E. , Jordan Stephen J.
Published: July 2021

Background

In men with nongonococcal urethritis (NGU), clinicians and patients rely on clinical cure to guide the need for additional testing/treatment and when to resume sex, respectively; however, discordant clinical and microbiological cure outcomes do occur. How accurately clinical cure reflects microbiological cure in specific sexually transmitted infections (STIs) is unclear.

Methods

Men with NGU were tested for Neisseria gonorrhoeae, Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), Trichomonas vaginalis, urethrotropic Neisseria meningitidis ST-11 clade strains, and Ureaplasma urealyticum (UU). Men received azithromycin 1 g and returned for a 1-month test-of-cure visit. In MG infections, we evaluated for the presence of macrolide resistance-mediating mutations (MRMs) and investigated alternate hypotheses for microbiological treatment failure using in situ shotgun metagenomic sequencing, phylogenetic analysis, multilocus sequence typing analyses, and quantitative PCR.

Results

Of 280 men with NGU, 121 were included in this analysis. In the monoinfection group, 52 had CT, 16 had MG, 7 had UU, 10 had mixed infection, and 36 men had idiopathic NGU. Clinical cure rates were 85% for CT, 100% for UU, 50% for MG, and 67% for idiopathic NGU. Clinical cure accurately predicted microbiological cure for all STIs, except MG. Discordant results were significantly associated with MG-NGU and predominantly reflected microbiological failure in men with clinical cure. Mycoplasma genitalium MRMs, but not MG load or strain, were strongly associated with microbiological failure.

Conclusions

In azithromycin-treated NGU, clinical cure predicts microbiological cure for all STIs, except MG. Nongonococcal urethritis management should include MG testing and confirmation of microbiological cure in azithromycin-treated MG-NGU when MRM testing is unavailable.
Sexually Transmitted Infection Epidemiology and Care in Rural Areas: A Narrative Review
Authors: Jenkins Wiley D. , Williams Leslie D. , Pearson William S.
Published: July 2021

Background

Although rural areas contain approximately 19% of the US population, little research has explored sexually transmitted infection (STI) risk and how urban-developed interventions may be suitable in more population-thin areas. Although STI rates vary across rural areas, these areas share diminishing access to screening and limited rural-specific testing of STI interventions.

Methods

This narrative review uses a political ecology model of health and explores 4 domains influencing STI risk and screening: epidemiology, health services, political and economic, and social. Articles describing aspects of rural STI epidemiology, screening access and use, and intervention utility within these domains were found by a search of PubMed.

Results

Epidemiology contributes to risk via multiple means, such as the presence of increased-risk populations and the at-times disproportionate impact of the opioid/drug use epidemic. Rural health services are diminishing in quantity, often have lesser accessibility, and may be stigmatizing to those needing services. Local political and economic influences include funding decisions, variable enforcement of laws/statutes, and systemic prevention of harm reduction services. Social norms such as stigma and discrimination can prevent individuals from seeking appropriate care, and also lessen individual self-efficacy to reduce personal risk.

Conclusions

Sexually transmitted infection in rural areas is significant in scope and facing diminished prevention opportunities and resources. Although many STI interventions have been developed and piloted, few have been tested to scale or operationalized in rural areas. By considering rural STI risk reduction within a holistic model, purposeful exploration of interventions tailored to rural environments may be explored.
Pelvic Inflammatory Disease Trends Among Emergency Department Visits in North Carolina, 2008 to 2017
Authors: Neo Dayna T. , Samoff Erika , Cope Anna
Published: July 2021

Background

Pelvic inflammatory disease (PID) is an infection of the upper female reproductive organs that can lead to infertility and ectopic pregnancies. It is a reportable condition in North Carolina (NC) but is likely underreported. We aimed to quantify PID diagnoses in NC emergency department (ED) visits.

Methods

The NC Disease Event Tracking and Epidemiology Collection Tool tracks all ED visits in NC. We identified PID diagnoses among women of reproductive age (15–44 years) between 2008 and 2017 using International Classification of Diseases, Ninth/Tenth Revision, Clinical Modification codes, and calculated the yearly proportion with PID diagnoses. We assessed the number of PID visits per patient each year, and the proportion of ED visits with a PID diagnosis by age, proportion of the patient's ZIP code living below the poverty line, insurance coverage, and NC provider region.

Results

The percent of women with PID decreased from 6189 (1.0%) in 2008 to 4337 (0.58%) in 2016 before increasing slightly to 4371 (0.61%) in 2017. We identified 54,502 (0.45%) ED visits among 51,847 (0.76%) women with ≥1 PID diagnosis code. Most (95.5%) women with PID had one ED visit during the calendar year. Each year, the proportion with PID was highest among women aged 20 to 24 years, covered under public insurance, from the most impoverished areas, and whose provider was in the Coastal region of NC.

Conclusions

The percent with PID among women visiting EDs decreased between 2008 and 2017 in NC. Although this decline was observed across all demographics, disparities associated with PID continued to persist over time.
Long-Term Increases in Mental Disorder Diagnoses After Invasive Mechanical Ventilation for Severe Childhood Respiratory Disease: A Propensity Matched Observational Cohort Study*
Authors: Geneslaw Andrew S. , Lu Yewei , Miles Caleb H. , Hua May , Cappell Joshua , Smerling Arthur J. , Olfson Mark , Edwards Jeffrey D. , Ing Caleb
Published: July 2021

OBJECTIVES:

To evaluate neurodevelopmental and mental disorders after PICU hospitalization in children requiring invasive mechanical ventilation for severe respiratory illness.

DESIGN:

Retrospective longitudinal observational cohort.

SETTING:

Texas Medicaid Analytic eXtract data from 1999 to 2012.

PATIENTS:

Texas Medicaid-enrolled children greater than or equal to 28 days old to less than 18 years old hospitalized for a primary respiratory illness, without major chronic conditions predictive of abnormal neurodevelopment.

INTERVENTIONS:

We examined rates of International Classification of Diseases, 9th revision–coded mental disorder diagnoses and psychotropic medication use following discharge among children requiring invasive mechanical ventilation for severe respiratory illness, compared with general hospital patients propensity score matched on sociodemographic and clinical characteristics prior to admission. Children admitted to the PICU for respiratory illness not necessitating invasive mechanical ventilation were also compared with matched general hospital patients as a negative control exposure.

MEASUREMENTS AND MAIN RESULTS:

Of 115,335 eligible children, 1,351 required invasive mechanical ventilation and were matched to 6,755 general hospital patients. Compared with general hospital patients, children requiring invasive mechanical ventilation had increased mental disorder diagnoses (hazard ratio, 1.43 [95% CI, 1.26–1.64]; p < 0.0001) and psychotropic medication use (hazard ratio, 1.67 [1.34–2.08]; p < 0.0001) following discharge. Seven-thousand seven-hundred eighty children admitted to the PICU without invasive mechanical ventilation were matched to 38,900 general hospital patients and had increased mental disorder diagnoses (hazard ratio, 1.08 [1.02–1.15]; p = 0.01) and psychotropic medication use (hazard ratio, 1.11 [1.00–1.22]; p = 0.049).

CONCLUSIONS:

Children without major comorbidity requiring invasive mechanical ventilation for severe respiratory illness had a 43% higher incidence of subsequent mental disorder diagnoses and a 67% higher incidence of psychotropic medication use. Both increases were substantially higher than in PICU patients with respiratory illness not necessitating invasive mechanical ventilation. Invasive mechanical ventilation is a life-saving therapy, and its application is interwoven with underlying health, illness severity, and PICU management decisions. Further research is required to determine which factors related to invasive mechanical ventilation and severe respiratory illness are associated with abnormal neurodevelopment. Given the increased risk in these children, identification of strategies for prevention, neurodevelopmental surveillance, and intervention after discharge may be warranted.
Overall Health Following Pediatric Critical Illness: A Scoping Review of Instruments and Methodology
Authors: Carlton Erin F. , Pinto Neethi , Smith McKenna , Fink Ericka L. , Watson R. Scott , Hoehn K. Sarah , Marupudi Neelima , Dervan Leslie A. , Lackey Mellanye , Ringwood Melissa , Maddux Aline B. ,   the POST-PICU Investigators of the PALISI Network and the Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network
Published: July 2021

OBJECTIVES:

Families identify overall health as a key outcome after pediatric critical illness. We conducted a planned secondary analysis of a scoping review to determine the methods, populations, and instruments used to evaluate overall health outcomes for both children and their families after critical illness.

DESIGN:

Planned Secondary Analysis of a Scoping Review.

SETTING:

We searched PubMed, EMBASE, PsycINFO, Cumulative Index of Nursing and Allied Health Literature, and the Cochrane Controlled Trials Registry databases from 1970 to 2017 to identify studies which measured postdischarge overall health of children who survived critical illness and their families.

Subjects:

Articles reporting overall health outcomes after pediatric critical illness.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Among the 407 articles which measured outcomes following pediatric critical illness, 161 (40%) measured overall health. The overall health domain was most commonly measured in traumatic brain injury (44%) and the general PICU populations (16%). In total, there were 39 unique measures used to evaluate overall health. Across all subjects, seven measures accounted for 89% of instruments, with the Glasgow Outcome Scale (47%) and the Pediatric Overall Performance Category (17%) being most commonly used. Excluding studies targeting survivors of traumatic brain injury, Pediatric Overall Performance Category, Glasgow Outcome Scale, and the General Health Questionnaire were the most commonly used instruments. Patients were followed for a median 10.5 months (interquartile range, 4.5–21 mo).

CONCLUSIONS:

Overall health was commonly assessed post-PICU discharge, especially in the traumatic brain injury population, using a heterogenous array of measures. Evaluation and consensus are imperative to identify the most appropriate method to measure overall health with the goal of improving care efficacy and facilitating recovery across populations of critically ill children.
The Use of Extracorporeal Life Support in Children With Immune-Mediated Diseases
Authors: Barreto Jessica A. , Mehta Amit , Thiagarajan Ravi R. , Hayward Kristen N. , Brogan Adrian , Brogan Thomas V.
Published: July 2021

OBJECTIVES:

To describe the use and outcomes of extracorporeal membrane oxygenation support among children with immune-mediated conditions.

DESIGN:

Retrospective cohort study.

SETTING:

The Extracorporeal Life Support Organization registry.

PATIENTS:

Patients 1 month to 18 years old with International Classification of Diseases, 9th Edition and International Classification of Diseases, 10th Edition codes for immune-mediated conditions from 1989 to 2018.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

During the study period, 207 patients with an immune-mediated condition received extracorporeal membrane oxygenation, and 50% survived to discharge. Most patients (63%) received extracorporeal membrane oxygenation for respiratory support with 53% survival, 21% received cardiac support (55% survival), and 15% received extracorporeal cardiopulmonary resuscitation (34% survival). The most common diagnosis among nonsurvivors was hemophagocytic lymphohistiocytosis/macrophage activation syndrome with 37% survival. Patients with juvenile idiopathic arthritis (23%) and dermatomyositis (25%) had the lowest survival. Nonsurvivors had a higher frequency of infections, neurologic complications, and renal replacement therapy use. Use of preextracorporeal membrane oxygenation corticosteroids was associated with mortality.

CONCLUSIONS:

Children with immune-mediated conditions can be successfully supported with extracorporeal membrane oxygenation. Extracorporeal membrane oxygenation use has increased over time, and survival varies considerably by diagnosis.
Socioeconomic Disadvantage and Distance to Pediatric Critical Care*
Authors: Brown Lauren E. , França Urbano L. , McManus Michael L.
Published: July 2021

OBJECTIVES:

To describe the geography of pediatric critical care services and the relationship between poverty and distance to these services across the United States.

DESIGN:

Retrospective, cross-sectional study.

SETTING:

Contiguous United States.

PATIENTS:

Children less than 18 years as represented in the 2016 American Community Survey.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Pediatric critical care services were geographically concentrated within urban areas, with half of all PICUs located within 9.5 miles of another (interquartile range, 3.4–51.5 miles). Median distances from neighborhoods to the nearest unit increased linearly with Area Deprivation Index (p < 0.001), such that the median distance from the least privileged neighborhoods was nearly three times that of the most privileged neighborhoods (first decile = 7.8 miles [interquartile range, 3.4–15.8 miles] vs tenth decile = 22.6 miles [interquartile range, 4.2–52.5 miles]; p < 0.001). A relationship between neighborhood poverty and distance to a PICU was present across all U.S. regions and within urban/suburban and rural areas.

CONCLUSIONS:

In the United States, the distance to pediatric critical care services increases with poverty. This carries implications for access to care and health outcome disparities.
Derivation and Validation of the Critical Bronchiolitis Score for the PICU
Authors: Mount Michael C. , Ji Xinge , Kattan Michael W. , Slain Katherine N. , Clayton Jason A. , Rotta Alexandre T. , Shein Steven L.
Published: July 2021

OBJECTIVES:

To derive and internally validate a bronchiolitis-specific illness severity score (the Critical Bronchiolitis Score) that out-performs mortality-based illness severity scores (e.g., Pediatric Risk of Mortality) in measuring expected duration of respiratory support and PICU length of stay for critically ill children with bronchiolitis.

DESIGN:

Retrospective database study using the Virtual Pediatric Systems (VPS, LLC; Los Angeles, CA) database.

SETTING:

One-hundred twenty-eight North-American PICUs.

PATIENTS:

Fourteen-thousand four-hundred seven children less than 2 years old admitted to a contributing PICU with primary diagnosis of bronchiolitis and use of ICU-level respiratory support (defined as high-flow nasal cannula, noninvasive ventilation, invasive mechanical ventilation, or negative pressure ventilation) at 12 hours after PICU admission.

INTERVENTIONS:

Patient-level variables available at 12 hours from PICU admission, duration of ICU-level respiratory support, and PICU length of stay data were extracted for analysis. After randomly dividing the cohort into derivation and validation groups, patient-level variables that were significantly associated with the study outcomes were selected in a stepwise backward fashion for inclusion in the final score. Score performance in the validation cohort was assessed using root mean squared error and mean absolute error, and performance was compared with that of existing PICU illness severity scores.

MEASUREMENTS AND MAIN RESULTS:

Twelve commonly available patient-level variables were included in the Critical Bronchiolitis Score. Outcomes calculated with the score were similar to actual outcomes in the validation cohort. The Critical Bronchiolitis Score demonstrated a statistically significantly stronger association with duration of ICU-level respiratory support and PICU length of stay than mortality-based scores as measured by root mean squared error and mean absolute error.

CONCLUSIONS:

The Critical Bronchiolitis Score performed better than PICU mortality-based scores in measuring expected duration of ICU-level respiratory support and ICU length of stay. This score may have utility to enrich interventional trials and adjust for illness severity in observational studies in this very common PICU condition.
Safety and antibody response to two-dose SARS-CoV-2 messenger RNA vaccination in persons with HIV
Authors: Ruddy Jake A. , Boyarsky Brian J. , Bailey Justin R. , Karaba Andrew H. , Garonzik-Wang Jacqueline M. , Segev Dorry L. , Durand Christine M. , Werbel William A.
Published: July 2021

This study of SARS-CoV-2 mRNA vaccination in 14 persons with HIV (PWH) demonstrated uniformly high anti-SARS-CoV-2 receptor binding domain (RBD) antibody titres after two doses, despite varied titres after a single dose. The majority of vaccine reactions were mild and no adverse events occurred.
Staphylococcus aureus infections in children
Authors: Cassat James E. , Thomsen Isaac
Published: July 2021

Purpose of review

Staphylococcus aureus is the most common invasive bacterial pathogen infecting children in the U.S. and many parts of the world. This major human pathogen continues to evolve, and recognition of recent trends in epidemiology, therapeutics and future horizons is of high importance.

Recent findings

Over the past decade, a relative rise of methicillin-susceptible S. aureus (MSSA) has occurred, such that methicillin-resistant S. aureus (MRSA) no longer dominates the landscape of invasive disease. Antimicrobial resistance continues to develop, however, and novel therapeutics or preventive modalities are urgently needed. Unfortunately, several recent vaccine attempts proved unsuccessful in humans.

Recent scientific breakthroughs highlight the opportunity for novel interventions against S. aureus by interfering with virulence rather than by traditional antimicrobial mechanisms. A S. aureus vaccine remains elusive; the reasons for this are multifactorial, and lessons learned from prior unsuccessful attempts may create a path toward an effective preventive. Finally, new diagnostic modalities have the potential to greatly enhance clinical care for invasive S. aureus disease in children.
Shigellosis in young children in low-income and middle-income countries: insights from molecular diagnostics
Authors: Platts-Mills James A. , Rogawski McQuade Elizabeth T.
Published: July 2021

Purpose of review

To describe the impact of molecular diagnostics on our understanding of the burden and epidemiology of shigellosis in children in low-income and middle-income countries.

Recent findings

The incorporation of molecular diagnostics has led to a substantial increase in estimates of the burden of shigellosis and have allowed for further resolution of other aspects of Shigella epidemiology, including the clinical characteristics of shigellosis, the association between clinical and subclinical Shigella infection and linear growth shortfalls, protection after natural infection, duration of convalescent shedding, and host determinants of susceptibility.

The increased sensitivity and precision afforded by molecular approaches has represented a major advance in our understanding of the epidemiology and burden of shigellosis in the settings of highest importance.
Cleft Lip and Palate Midfacial Hypoplasia: Criteria to Choose the Treatment
Authors: Fariña Rodrigo , Lolas Jorge , Moreno Emilio , Alister Juan Pablo , Uribe María Francisca , Pantoja Roberto , Valladares Salvador , Arrué Camila
Published: July 2021

A series of skeletal and dentoalveolar/occlusal criteria were proposed for choosing the treatment modality for the management of midface hypoplasia in cleft lip/palate patients, focusing on functional improvement, aesthetics, and minimizing the risk of recurrence and secondary alterations. For which, 42 patients with nonsyndromic cleft lip/palate, all with previous primary lip/palate surgeries and without previous osteotomies, were analyzed. Orthognathic surgery (OS) (n = 24) and maxillary distraction osteogenesis (n = 18) with anterior segmental osteotomies (segmental distraction osteogenesis [SD]), alveolar transport disc (TD), and midface total distraction osteogenesis (TDO) by modified Le Fort III osteotomy was done.

The average of maxillary advancement for OS was 5.58 ± 0.83 mm, for SD 9.4 ± 0.89 mm, for TD 8.00 ± 1.00 mm, and for TDO was 8.13 ± 1.55 mm.

In the presence of infraorbital and/or zygomatic hypoplasia, TDO was performed using skeletal anchorage, with the requirement of occlusal stability in dental cast in occlusion. In short maxillary arch without dental cast feasibility in occlusion, hypodontia/agenesis or absence of premaxilla, TD and SD was performed. There was only 1 mm of recurrence in 1 patient of each group. Changes in speech were detected in 2 patients in the OS group (8.3%). Orthognathic surgery can be indicated for advancements ≤7 mm not requiring orbito-zygomatic advancement, whereas distraction osteogenesis can be indicated for advances >8 mm with or without the need for orbito-zygomatic advancement, in addition with other dentoalveolar factors and velopharyngeal function.
Effect of Cleft Width on the Outcome of Presurgical Nasoalveolar Molding in Patients With Unilateral Cleft Lip and Palate
Authors: Titiz Serap , Aras Aynur
Published: July 2021

The purpose of this study was to investigate the short-term effects of presurgical nasoalveolar molding (PNAM) according to cleft width (CW) in patients with unilateral cleft lip and palate (UCLP). In this retrospective study, 32 newborns with nonsyndromic UCLP treated with PNAM were allocated to 2 groups based on CW (group A, CW ≤5 mm; and group B, CW >5 mm). The following measurements were carried out using standardized photographs taken before and after PNAM therapy (before primary lip surgery): nostril axis inclination of healthy (NAI-NC) and cleft sides (NAI-C), columellar angle (CA), nasal base inclination (NBI), nasal floor width ratio (NFWR), alar base height ratio (ABHR), and columellar length ratio. Before PNAM therapy, there were significant differences between the 2 groups with respect to NAI-C, NBI, NFWR, and ABHR, indicating greater deformation of the nose in group B. After PNAM therapy, CA, NAI-C, NAI-NC, NFWR, and columellar length ratio were significantly improved in both the groups, whereas NBI and ABHR significantly worsened in group B. The improvement in CA, NAI-C, and NFWR was significantly greater in group B. Although a larger CW had some negative effects on the outcome of PNAM, it was found to be advantageous for nasal symmetry, if initiated as early as possible. Nevertheless, it is important to consider those aspects of the nasolabial area that are involved in the perception of symmetry when evaluating the effect of CW on PNAM outcomes in UCLP.
Death-Associated Protein Kinase 1 Promotes Alveolar Epithelial Cell Apoptosis and Ventilator-Induced Lung Injury Through P53 Pathway
Authors: Wang Yaxin , Fang Xiangzhi , Yang Yiyi , Chen Lin , Xiong Wei , Song Limin , Li Bo , Zhou Ting , Yu Yuan , Yang Xiaobo , Shu Huaqing , Yuan Shiying , Yao Shanglong , Shang You
Published: July 2021

Objectives:

Mechanical stretch-induced alveolar epithelial cell (AEC) apoptosis participates in the onset of ventilator-induced lung injury (VILI). In this study, we explored whether death-associated protein kinase 1 (DAPK1) mediated cyclic stretch (CS)-induced AEC apoptosis and VILI though P53 pathway.

Materials and Methods:

AEC apoptosis was induced by CS using the FX-5000T Flexercell Tension Plus system. C57BL/6 mouse received high tidal volume ventilation to build VILI model. DAPK1 inhibitor, P53 inhibitor, or DAPK1 plasmid was used to regulate the expression of DAPK1 and P53, respectively. Flow cytometery was performed to assay cell apoptosis and the changes of mitochondrial membrane potential (MMP); immunoblotting was adopted to analyze related protein expression. The binding of related proteins was detected by coimmunoprecipitation; AEC apoptosis in vivo was determined by immunohistochemistry assay.

Results:

CS promoted AEC apoptosis, increased DAPK1 and P53 expression, and induced the binding of DAPK1 and P53; inhibition of DAPK1 or P53 reduced CS-induced AEC apoptosis, suppressed the expression of Bax, increased Bcl-2 level, and stabilized MMP; AEC apoptosis and the level of P53 were both increased after overexpressing of DAPK1. Moreover, DAPK1 plasmid transfection also promoted the expression of Bax and the change of MMP, but decreased the level of Bcl-2. Inhibition of DAPK1 or P53 in vivo alleviated high tidal volume ventilation-induced AEC apoptosis and lung injury.

Conclusions:

DAPK1 contributes to AEC apoptosis and the onset of VILI though P53 and its intrinsic pro-apoptotic pathway. Inhibition of DAPK1 or P53 alleviates high tidal volume ventilation-induced lung injury and AEC apoptosis.
Gastroesophageal Reflux Disease Outcomes After Vertical Sleeve Gastrectomy and Gastric Bypass
Authors: Leslie Daniel , Wise Eric , Sheka Adam , Abdelwahab Hisham , Irey Ryan , Benner Ashley , Ikramuddin Sayeed
Published: July 2021

Objective:

The objective of this study is to assess whether vertical sleeve gastrectomy (VSG) increases the incidence of gastroesophageal reflux disease (GERD), esophagitis and Barrett esophagus (BE) relative to patients undergoing Roux-en-Y gastric bypass (RYGB) in patients with and without preoperative GERD.

Summary of Background Data:

Concerns for potentiation of GERD, supported by multiple high-quality retrospective studies, have hindered greater adoption of the VSG.

Methods:

From the OptumLabs Data Warehouse, VSG and RYGB patients with ≥2 years enrollment were identified and matched by follow-up time. GERD [reflux esophagitis, prescription for acid reducing medication (Rx) and/or diagnosis of BE], upper endoscopy (UE), and re-admissions were evaluated beyond 90 days.

Results:

A total of 8362 patients undergoing VSG were matched 1:1 to patients undergoing RYGB, on the basis of post-operative follow-up interval. Age, sex, and follow-up time were similar between the 2 groups (P > 0.05). Among all patients, postoperative GERD was more frequently observed in VSG patients relative to RYGB patients (60.2% vs 55.6%, respectively; P < 0.001), whereas BE was more prevalent in RYGB patients (0.7% vs 1.1%; P = 0.007). Postoperatively, de novo esophageal reflux symptomatology was more common in VSG patients (39.3% vs 35.3%; P < 0.001), although there was no difference in development of the histologic diagnoses reflux esophagitis and BE. Furthermore, postoperative re-admission was higher in the RYGB cohort (38.9% vs 28.9%; P < 0.001).

Conclusions:

Compared to RYGB, VSG may not have inferior long-term GERD outcomes, while also leading to fewer re-hospitalizations. These data challenge the prevailing opinion that patients with GERD should undergo RYGB instead of VSG.
Expanding the Donor Pool: First Use of Hepatitis B Virus Nat Positive Solid Organ Allografts Into Seronegative Recipients
Authors: Delman Aaron M. , Turner Kevin M. , Safdar Kamran , Anwar Nadeem , Silski Latifa S. , Lee Tiffany C. , Luckett Keith , Cuffy Madison C. , Quillin Ralph C. , Schoech Michael , Kaiser Tiffany E. , Govil Amit , Bari Khurram , Shah Shimul A.
Published: July 2021

Objectives:

The aim of this study was to assess the 1-year safety and effectiveness of HBV Nucleic Acid Test positive (HBV NAT+) allografts in seronegative kidney transplant (KT) and liver transplant (LT) recipients.

Summary Background Data:

Despite an ongoing organ shortage, the utilization of HBV NAT+ allografts into seronegative recipients has not been investigated.

Methods:

From January 2017 to October 2020, a prospective cohort study was conducted among consecutive KT and LT recipients at a single institution. Primary endpoints were post-transplant HBV viremia, graft and patient survival.

Results:

With median follow-up of 1-year, there were no HBV-related complications in the 89 HBV NAT+ recipients. Only 9 of 56 KTs (16.1%) and 9 of 33 LTs (27.3%) experienced post-transplant HBV viremia at a median of 185 (KT) and 269 (LT) days postoperatively. Overall, viremic episodes resolved to undetected HBV DNA after a median of 80 days of entecavir therapy in 16 of 18 recipients. Presently, 100% of KT recipients and 93.9% of LT recipients are HBV NAT− with median follow-up of 13 months, whereas 0 KT and 8 LT (24.2%) recipients are HBV surface antigen positive indicating chronic infection. KT and LT patient and allograft survival were not different between HBV NAT+ and HBV NAT− recipients (P > 0.05), whereas HBV NAT+ KT recipients had decreased waitlist time and pretransplant duration on dialysis (P < 0.01).

Conclusions:

This is the largest series describing the transplantation of HBV NAT+ kidney and liver allografts into HBV seronegative recipients without chronic HBV viremia or decreased 1-year patient and graft survival. Increasing the utilization of HBV NAT+ organs in nonviremic recipients can play a role in decreasing the national organ shortage.
Open-source mapping and variant calling for large-scale NGS data from original base-quality scores
Authors: Krasheninina Olga , Hwang Yih-Chii , Bai Xiaodong , Zalcman Aleksandra , Maxwell Evan , Reid Jeffrey G. , Salerno William J.
Published: July 2021

Abstract

Standardized genome informatics protocols minimize reprocessing costs and facilitate harmonization across studies if implemented in a transparent, accessible and reproducible manner. Here we define the OQFE protocol, a lossless read-mapping protocol that retains key features of existing NGS standard methods. We demonstrate that variants can be called directly from NovaSeq OQFE data without the need for base quality score recalibration and describe a large-scale variant calling protocol for OQFE data. The OQFE protocol is open-source and a containerized implementation is provided.
Comparative genomics supports that Brazilian bioethanolSaccharomyces cerevisiaecomprise a unified group of domesticated strains related to cachaça spirit yeasts
Authors: Jacobus Ana Paula , Stephens Timothy G. , Youssef Pierre , González-Pech Raul , Chen Yibi , Basso Luiz Carlos , Frazzon Jeverson , Chan Cheong Xin , Gross Jeferson
Published: July 2021

Ethanol production from sugarcane is a key renewable fuel industry in Brazil. Major drivers of this alcoholic fermentation areSaccharomyces cerevisiaestrains that originally were contaminants to the system and yet prevail in the industrial process. Here we present newly sequenced genomes (using Illumina short-read and PacBio long-read data) of two monosporic isolates (H3 and H4) of theS. cerevisiaePE-2, a predominant bioethanol strain in Brazil. The assembled genomes of H3 and H4, together with 42 draft genomes of sugarcane-fermenting (fuel ethanol plus cachaça) strains, were compared against those of the reference S288c and diverseS. cerevisiae. All genomes of bioethanol yeasts have amplifiedSNO2(3)/SNZ2(3)gene clusters for vitamin B1/B6 biosynthesis, and display ubiquitous presence ofSAM-dependent methyl transferases, a gene family rare inS. cerevisiae. Widespread amplifications of quinone oxidoreductasesYCR102C/YLR460C/YNL134C, and the structural or punctual variations among aquaporins and components of the iron homeostasis system, likely represent adaptations to industrial fermentation. Interesting is the pervasive presence among the bioethanol/cachaça strains of a five-gene cluster (Region B) that is a known phylogenetic signature of European wine yeasts. Combining genomes of H3, H4, and 195 yeast strains, we comprehensively assessed whole-genome phylogeny of these taxa using an alignment-free approach. The 197-genome phylogeny substantiates that bioethanol yeasts are monophyletic and closely related to the cachaça and wine strains. Our results support the hypothesis that biofuel-producing yeasts in Brazil may have been co-opted from a pool of yeasts that were pre-adapted to alcoholic fermentation of sugarcane for the distillation of cachaça spirit, which historically is a much older industry than the large-scale fuel ethanol production.
Comparative phytotoxicity and chironomid toxicity assessments of leaf successive extract fractions of Asiatic poison bulb,Crinum asiaticumL
Authors: Goswami Souren , Ray Sanjib
Published: July 2021

Crinum asiaticumis an evergreen bulbous perennial shrub of Amaryllidaceae family with ethnomedicinal importance and our earlier study described a comparative account antimicrobial and antioxidant properties of the different solvent-mediated sequential extract fractions. The present study aimed to analyze their comparative account of induced phytotoxicity and chironomid toxicity. For phytotoxicity assessment, germination inhibition and seedling’s root and shoot growth retardation effects onTriticum aestivum and Cicer arietinumwere analyzed and for lethal concentration determination, the freshwater bottom-dwelling first instars chironomid larvae were used. The crude aqueous, petroleum ether and ethyl acetate extracts showed significant toxic effects on both meristematic tissue and aquatic midges. The phytotoxic assays indicate that the ethyl acetate fraction contains the most potent growth inhibitors, followed by the crude aqueous and petroleum ether fractions. The last aqueous fraction was found to be the least toxic, the highest LC50and LT50values and ethyl acetate extract fraction having highest toxicity. Thus the present study supplements to our earlier report, that indicated the last aqueous extract fraction ofC. asiaticumhas potent antioxidant and antibacterial potentials as well as its prospective use in livestock maintenance, as it is least toxic and the ethyl acetate extract, the most toxic fraction identified here, is needed to explore for pharmaceutical importance.
Neural evidence for categorical biases in working memory for location and orientation
Authors: Bae Gi-Yeul
Published: July 2021

Previous research demonstrated that visual working memory exhibits biases with respect to the categorical structure of the stimulus space. However, a majority of those studies used behavioral measures of working memory, and it is not clear whether the working memory representations per se are influenced by the categorical structure or whether the biases arise in decision or response processes during the report. Here, I applied a multivariate decoding technique to EEG data collected during working memory tasks to determine whether neural activity associated with the working memory representation is categorically biased prior to the report. I found that the decoding of spatial working memory was biased away from the nearest cardinal location, consistent with the biases observed in the behavioral responses. In a follow-up experiment which was designed to prevent the use of a response preparation strategy, I found that the decoding still exhibited categorical biases. Together, these results provide neural evidence that working memory representations themselves are categorically biased, imposing important constraints on the computational models of working memory representations.
TranSuite: a software suite for accurate translation and characterization of transcripts
Authors: Entizne Juan C. , Guo Wenbin , Calixto Cristiane P.G. , Spensley Mark , Tzioutziou Nikoleta , Zhang Runxuan , Brown John W.S.
Published: July 2021

Protein translation programs often select the longest open reading frame (ORF) in a transcript leading to numerous inaccurate and mis-annotated ORFs in databases. Unproductive transcript isoforms containing premature termination codons (PTCs) are potential substrates for nonsense-mediated decay (NMD). These transcripts often contain truncated ORFs but are incorrectly annotated due to selection of a long ORF beginning at an AUG downstream of the PTC despite the transcript containing the authentic translation start AUG. In gene expression and alternative splicing analyses, it is important to identify transcript isoforms which code for different protein variants and to distinguish these from potential NMD substrates. Here, we present TranSuite, a pipeline of bioinformatics tools that address these challenges by performing accurate translations, characterizing alternative ORFs and identifying NMD and other features of transcripts in newly assembled and existing transcriptomes. Directly comparing ORFs defined by TranSuite and TransDecoder for the Arabidopsis transcriptome AtRTD2 identified ORF mis-calling in over 16k (27%) of transcripts by TransDecoder.
Mechanism through which retrocyclin targets flavivirus multiplication
Authors: Jia Xiaoying , Guo Jiao , Yuan Weirong , Sun Lingling , Liu Yang , Zhou Minmin , Xiao Gengfu , Lu Wuyuan , Garzino-Demo Alfredo , Wang Wei
Published: July 2021

Currently, there are no approved drugs for the treatment of flavivirus infection. Accordingly, we tested the inhibitory effects of the novel θ-defensin retrocyclin-101 (RC-101) against flavivirus infection, and investigated the mechanism underlying the potential inhibitory effects. First, RC-101 robustly inhibited both Japanese encephalitis virus (JEV) and Zika virus (ZIKV) infections. RC-101 exerted inhibitory effects on the entry and replication stages. Results also indicated that the non-structural protein NS2B-NS3 serine protease might serve as a potential viral target. Further, RC-101 inhibited protease activity at the micromolar level. We also demonstrated that with respect to the glycoprotein E protein of flavivirus, the DE loop of domain III, which is the receptor-binding domain of the E protein, might serve as another viral target of RC-101. Moreover, a JEV DE mutant exhibited resistance to RC-101, which was associated with deceased binding affinity of RC-101 to DIII. These findings provide a basis for the development of RC-101 as a potential candidate for the treatment of flavivirus infection.

Importance

RC has been reported to have a broad-spectrum antimicrobial activity. In this study, we firstly report that RC-101 could inhibit ZIKV and JEV infections. Moreover, both the NS2B-NS3 serine protease and the DE loop in the E glycoprotein might serve as the viral targets of RC-101.
Screening, Identification and Growth Promotion Ability of Phosphate Solubilizing Bacteria from Soybean Rhizosphere under Maize-Soybean Intercropping Systems
Authors: Wang Wenjing , Sarpong Clement Kyei , Song Chun , Zhang Xiaofeng , Gan Yuefeng , Wang Xiaochun , Yong Taiwen , Chang Xiaoli , Wang Yu , Yang Wenyu
Published: July 2021

The solubilization and mineralization of phosphorus by phosphate-solubilizing bacteria (PSB) is one of the most important bacterial physiological characteristics in the soil biogeochemical cycle. Through the isolation and screening of microorganisms in the rhizosphere soil of intercropped soybean in Ya’an, Renshou and Chongzhou, 9 PSBs with high phosphorus solubilizing ability were identified. It mainly belongs toBacillusandPseudomonas. The phosphate solubility ofBacillus aryabhattaiB8W22 is as high as 388.62 µg·mL-1. The physiological and biochemical characteristics of each strain showed that it can secrete organic acids such as formic acid, acetic acid lactic acid and pyruvic acid. In addition, all strains can produce indole acetic acid and siderophores that promote plant growth. Seed germination experiments also showed that the phosphorus solubilizing bacteria isolated in this research have a certain ability to promote plant growth.

IMPRTANCE

Bacillus aryabhattaifrom rhizosphere soil of intercropped soybean has high phosphate-solubilizing ability, could produce indole acetic acid and siderophores that promote plant growth, and are of great significance in reducing the application of chemical phosphate fertilizers and promoting sustainable agricultural development.
Evaluation of the effect of life extension of DHEA extract from sweet potato onCaenorhabditis elegans
Authors: Chen Huan , Zou Dan , Wang Lufeng , Huang Junyi
Published: July 2021

Products from natural sources are being used from centuries. This study investigates the potential antiaging activity of DHEA extracts from sweet potato. DHEA was extracted with the assistance of acid hydrolysis-ultrasonic, and theCaenorhabditis elegansmodel was used to investigate the antiaging activity. The results from the current study articulated that DHEA from sweet potato in 50 μmol / L effectively prolonged the life-span ofC. elegansby 13.60%, but the effect was not concentration-dependent. Besides, DHEA had no effect on the growth ofE. coliOP50and the nematode pharyngeal pump rate, indicating that DHEA didn’t delay the aging of the nematode through calorie restriction. Further experiments demonstrated that DHEA would slow the growth of nematode body size, reduce the accumulation of ROS and lipofuscin ofC. elegans. The expression and migration ofdaf-16into the nucleus of nematode were significantly improved as well. The antiaging effect of DHEA onC. elegansmay be achieved by strengthening the nematode’s ability to resist oxidative stress and promoting nuclear expression of thedaf-16gene.

Summary Statement

This study proved that DHEA from sweet potato can extended lifespan ofCaenorhabditis elegansinduced by strengthening the antioxidant capacity and promoting the nuclear expression ofdaf-16
Paracrine signalling between intestinal epithelial and tumour cells induces a regenerative programme
Authors: Jacquemin Guillaume , Wurmser Annabelle , Huyghe Mathilde , Sun Wenjie , Homayed Zeinab , Merle Candice , Perkins Meghan , Qasrawi Fairouz , Richon Sophie , Dingli Florent , Arras Guillaume , Loew Damarys , Vignjevic Danijela , Pannequin Julie , Fre Silvia
Published: July 2021

Tumours are complex ecosystems composed of different types of cells that communicate and influence each other. While the critical role of stromal cells in affecting tumour growth is well established, the impact of mutant cancer cells on healthy surrounding tissues remains poorly defined. Here, we uncovered a paracrine mechanism by which intestinal cancer cells reactivate foetal and regenerative Yap-associated transcriptional programs in neighbouring wildtype epithelial cells, rendering them adapted to thrive in the tumour context. We identified the glycoprotein Thrombospondin-1 (THBS1) as the essential factor that mediates non-cell autonomous morphological and transcriptional responses. Importantly, Thbs1 is associated with bad prognosis in several human cancers. This study reveals the THBS1-YAP axis as the mechanistic link mediating paracrine interactions between epithelial cells in intestinal tumours.
Valproic acid stimulates myogenesis in pluripotent stem cell–derived mesodermal progenitors in a Notch-dependent manner
Authors: Breuls Natacha , Giarratana Nefele , Yedigaryan Laura , Carai Paolo , Heymans Stephane , Ranga Adrian , Deroose Christophe M. , Sampaolesi Maurilio
Published: July 2021

Muscular dystrophies are debilitating neuromuscular disorders for which no cure exists. As this disorder affects both cardiac and skeletal muscle, patients would benefit from a cellular therapy that can simultaneously regenerate both tissues. The current protocol to derive bipotent mesodermal progenitors which can differentiate into cardiac and skeletal muscle relies on the spontaneous formation of embryoid bodies, thereby hampering further clinical translation. Additionally, as skeletal muscle is the largest organ in the human body, a high myogenic potential is necessary for successful regeneration. Here, we have optimized a protocol to generate chemically defined induced pluripotent stem cell-derived mesodermal progenitors (cdMiPs). We demonstrate that these cells contribute to myotube formation and differentiate into cardiomyocytes, both in vitro and in vivo. Furthermore, the addition of valproic acid, a clinically approved small molecule, increases the potential of the cdMiPs to contribute to myotube formation without compromising their ability to differentiate towards cardiomyocytes. This effect is mediated through the activation of the Notch signaling pathway. Taken together, these results constitute a novel approach to generate mesodermal progenitors with enhanced myogenic potential using clinically approved reagents, which opens the door to new therapeutic solutions in the treatment of muscular dystrophy.
TetrODrive: An open-source microdrive for combined electrophysiology and optophysiology
Authors: Brosch Marcel , Vlasenko Alisa , Ohl Frank W. , Lippert Michael T.
Published: July 2021

Objective

In tetrode recordings, the cell types of the recorded units are difficult to determine based on electrophysiological characteristics alone. Optotagging, the use of optogenetic stimulation at the tip of electrodes to elicit spikes from genetically identified cells, is a method to overcome this challenge. However, recording from many different cells requires advancing electrodes and light sources slowly through the brain with a microdrive. Existing designs suffer from a number of drawbacks, such as limited stability and precision, high cost, complex assembly, or excessive size and weight.

Approach

We designed TetrODrive as a microdrive that can be 3D printed on an inexpensive desktop resin printer and has minimal parts, assembly time, and cost. The microdrive can be assembled in 15 minutes and the price for all materials, including the 3D printer, is lower than a single commercial microdrive. To maximize recording stability, we mechanically decoupled the drive mechanism from the electrical and optical connectors.

Main results

The developed microdrive is small and light enough to be carried effortlessly by a mouse. It provides high signal-to-noise ratio recordings from optotagged units, even across recording sessions. Owing to its moveable optical fiber, our microdrive can also be used for fiber photometry. We evaluated our microdrive by recording single units and calcium signals in the ventral tegmental area (VTA) of mice and confirmed cell identity via optotagging. Thereby we found units not following the classical reward prediction error model.

Significance

TetrODrive is a tiny, lightweight, and affordable microdrive for optophysiology in mice. Its open design, price, and built-in characteristics can significantly expand the use of microdrives in mice.