bluuebunny/crossref_metadata_2025 huggingface dataset:
New ZNF469 Mutations in Spanish Siblings With Brittle Cornea Syndrome
Authors: García de Oteyza Gonzalo , Fernández Engroba Jorge , Charoenrook Victor
Published: April 2023

Purpose:

The aim of this study was to describe the clinical, tomographic, and genetic findings of 2 Spanish siblings with brittle cornea syndrome and report a new mutation of gene ZNF469 implicated in the development of this disorder.

Methods:

In this study, 2 male siblings who had been diagnosed with brittle cornea syndrome underwent ophthalmologic and genetic assessment.

Results:

A novel homozygous deletion c.2972del, p.(Pro991Hisfs62) in the ZNF469 gene was identified in a Spanish family.

Conclusions:

This is the first report of a ZNF469 mutation in a Spanish family causing brittle cornea syndrome. The discovery of this new mutation amplifies the spectrum of ZNF469 variants implicated in this syndrome.
Clinical applications of bioengineered tissue-cellular products for management of corneal diseases
Authors: Tran Tu M. , Hou Joshua H.
Published: April 2023

Purpose of review

To discuss bioengineered tissue-cellular products for treatment of corneal diseases that are currently in clinical use. These include tissue-cellular products that have received regulatory approval, are being used off-label in clinical practice, or are in active use in clinical trials.

Recent findings

Due to the global shortage of donor corneal tissue, significant efforts have been made to develop bioengineering tissue-cellular products that can replace or augment the use of cadaveric tissue for corneal transplantation. The development of carrier substrates to support transplantation of cultivated limbal epithelial transplantation (CLET) has been a growing area of research. CLET offers a promising therapeutic alternative to conventional simple limbal epithelial transplantation and keratolimbal allografts for treatment of limbal stem cell deficiency. Engineered tissue matrices and porcine-derived corneas are potential alternatives to human donor tissue in anterior lamellar keratoplasty for corneal ulcers and scars, as well as intrastromal transplants for advanced keratoconus. For endothelial disease, substrate supported cultured endothelial cell grafts, and synthetic barrier devices are promising alternative to traditional endothelial keratoplasties.

There has been increasing interest in cellular and acellular bioengineered tissue-cellular and synthetic products for treatment of corneal diseases, and many of these products have already seen clinical use. Industry and academia have important roles in advancing these products to later phase clinical trials and comparing them to conventional allograft approaches. Future development of full thickness donor corneas with cultivated epithelium, endothelium, and stromal keratocytes in a biosynthetic matrix will likely be an important next step in tissue alternatives. Continued progress in this field will be critical for addressing the global disease burden from corneal blindness.
Expanding indications for corneal cross-linking
Authors: Hafezi Farhad , Torres-Netto Emilio A. , Hillen Mark
Published: April 2023

Purpose of review

The aim of this study was to summarize the recent developments in corneal cross-linking (CXL) and its indications, including corneal ectasias, refractive surgery and infectious keratitis.

Recent findings

Advances in CXL technology, such as the use of higher-intensity LED ultraviolet (UV) light sources and a better understanding of the UV-riboflavin photochemical reaction, have enabled safer and more effective methods of cross-linking thin and ultra-thin corneas, and more effective accelerated transepithelial/‘epi-on’ CXL procedures that are beginning to supplant the Dresden protocol as the ‘gold standard’ CXL method. CXL is also being used in combination with laser surgery, not only to expand the patient base who can receive refractive surgery, but also to help rehabilitate vision in patients with ectasia. CXL, and CXL combined with photorefractive keratectomy (PRK), can result in corneal flattening of 1–2 D, and corneal regularization of 4–5 D, respectively. Finally, photoactivated chromophore for keratitis-corneal cross-linking (PACK-CXL) has been shown to be an effective therapy for infectious keratitis, both alone, and in combination with antimicrobial drugs.

CXL has evolved from a single technique to treat a single corneal ectasia, keratoconus, to several techniques with several indications, spanning a spectrum of corneal ectasias, as well as visual rehabilitation, refractive procedures and infectious keratitis treatment.
Influence and predictive value of optional parameters in new-generation intraocular lens formulas
Authors: Wendelstein Jascha A. , Rothbächer Jan , Heath Michael , McDonald Michael C. , Hoffmann Peter C. , Cooke David L. , Seiler Theo G. , Langenbucher Achim , Riaz Kamran M.
Published: April 2023

Purpose:

To evaluate the accuracy of various variations of new-generation multivariate intraocular lens (IOL) power calculation using the Barrett Universal II, Castrop, Emmetropia Verifying Optical 2.0, Hill–Radial Basis Function 3.0, Kane, and PEARL-DGS formulas with and without optional biometric parameters.

Setting:

Tertiary care academic medical center.

Design:

Retrospective case series. Single-center study.

Methods:

Inclusion of patients after uneventful cataract surgery implanting AU00T0 IOLs. Data from one eye per patient were randomly included. Eyes with a corrected distance visual acuity worse than 0.1 logMAR were excluded. IOLCON-optimized constants were used for all formulas other than the Castrop formula. The outcome measures were prediction error (PE) and absolute prediction error (absPE) for the 6 study formulas.

Results:

251 eyes from 251 patients were assessed. Excluding lens thickness led to statistically significant differences in absPE in several formulas. Leaving out horizontal corneal diameter did not impact absPE in several formulas. Differences in PE offset were observed between the various formula variations.

Conclusions:

When using multivariate formulas with an A-constant, including certain optional parameters is vital for optimal refractive results. Formula variations excluding certain biometric parameters need specifically optimized constants and do not perform similarly when using the constant of the respective formula using all parameters.
Patient demographics, tumor characteristics, and outcomes following surgical treatment of benign and malignant brachial plexus tumors: a systematic review
Authors: Shekouhi Ramin , Chim Harvey
Published: April 2023

Background:

Various treatment options have been introduced for the management of primary tumors of the brachial plexus (BP), ranging from conservative therapy to wide local excision with/without postoperative chemoradiotherapy. However, no consensus exists regarding optimal treatment strategies based on collated and published data.

Objective:

The aim of this study was to investigate the clinicopathological characteristics and outcome of patients with primary tumors of the BP who underwent surgical treatment.

Data sources:

A systematic search of the four main online databases, including Web of Science (WOS), PubMed, Scopus, and Google Scholar, was conducted.

Study selection:

All related articles addressing the clinical outcome and role of surgical interventions for management of primary tumors of the BP.

Intervention:

Optimal surgical and radiotherapeutic interventions for benign and malignant lesions based on the pathologic characteristics and location of primary BP tumors.

Results:

A total of 687 patients (693 tumors) with a mean age of 41.7±8.7 years old were evaluated. In total, 629 (90.8%) tumors were benign, and 64 (9.2%) were malignant, with a mean tumor size of 5.4±3.1 cm. The location of the tumor was reported for 639 patients. For these tumors, 444 (69.5%) originated from the supraclavicular region, and 195 (30.5%) were infraclavicular. The trunks were the most common location for tumor involvement, followed by the roots, cords, and terminal branches. Gross total resection was achieved in 432 patients and subtotal resection (STR) was performed in 109 patients. With neurofibromas, STR still resulted in good outcomes. The outcomes following treatment of malignant peripheral nerve sheath tumors were poor regardless of the type of resection. In general, symptoms related to pain and sensory issues resolved rapidly postoperatively. However, the resolution of motor deficits was often incomplete. Local tumor recurrence occurred in 15 (2.2%), patients and distant metastasis was observed in only eight (1.2%) cases. The overall mortality was 21 (3.1%) patients among the study population.

Limitations:

The main limitation was the lack of level I and II evidence.

Conclusions:

The ideal management strategy for primary BP tumors is complete surgical resection. However, in some cases, particularly for neurofibromas, STR may be preferable to preserve maximal neurological function. The degree of surgical excision (total or subtotal) mainly depends on the pathological characteristics and primary location of the tumor.
Comparison between minimally invasive partial nephrectomy and open partial nephrectomy for complex renal tumors: a systematic review and meta-analysis
Authors: Li Kun-peng , Chen Si-yu , Wang Chen-yang , Yang Li
Published: April 2023

Background:

The present study aimed to conduct a pooled analysis to compare the efficacy and safety of minimally invasive partial nephrectomy (MIPN) with open partial nephrectomy (OPN) in patients with complex renal tumors (defined as PADUA or RENAL score ≥7).

Methods:

The present study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, Supplemental Digital Content 1, http://links.lww.com/JS9/A394. We conducted a systematic search of the PubMed, Embase, Web of Science, and Cochrane Library databases until October 2022. MIPN and OPN-controlled trials for complex renal tumors were included. The primary outcomes were perioperative results, complications, renal function, and oncologic outcomes.

Results:

A total of 2405 patients were included in 13 studies. MIPN outperformed OPN in terms of hospital stay [weighted mean difference (WMD) −1.84 days, 95% CI −2.35 to −1.33; P<0.00001], blood loss (WMD −52.42 ml, 95% CI −71.43 to −33.41; P<0.00001), transfusion rates [odds ratio (OR) 0.34, 95% CI 0.17–0.67; P=0.002], major complications (OR 0.59, 95% CI 0.40–0.86; P=0.007) and overall complications (OR 0.43, 95% CI 0.31–0.59; P<0.0001), while operative time, warm ischemia time, conversion to radical nephrectomy rates, estimated glomerular decline, positive surgical margins, local recurrence, overall survival, recurrence-free survival, and cancer-specific survival were not significantly different.

Conclusions:

The present study demonstrated that MIPN was associated with a shorter length of hospital stay, less blood loss, and fewer complications in treating complex renal tumors. MIPN may be considered a better treatment for patients with complex tumors when technically feasible.
Transdermal Detection of MB-102 and Correlation to Meropenem Pharmacokinetics During Continuous Renal Replacement Therapy: In Vivo Results
Authors: Dorshow Richard B. , Johnson James R. , Shieh Jeng-Jong , Riley I. Rochelle , Rogers Thomas E. , Pino Christopher J. , Johnston Kimberly A. , Tang Peter , Nolin Thomas D. , Humes H. David , Goldstein Stuart L.
Published: April 2023

Critically ill patients undergoing continuous renal replacement therapy (CRRT) have medical conditions requiring extensive pharmacotherapy. Continuous renal replacement therapy impacts drug disposition. Few data exist regarding drug dosing requirements with contemporary CRRT modalities and effluent rates. The practical limitations of pharmacokinetic studies requiring numerous plasma and effluent samples, and lack of generalizability of observations from specific CRRT prescriptions, highlight gaps in bedside assessment of CRRT drug elimination and individualized dosing needs. We employed a porcine model using transdermal fluorescence detection of the glomerular filtration rate fluorescent tracer agent MB-102, with the aim to assess the relationship between systemic exposure of MB-102 and meropenem during CRRT. Animals underwent bilateral nephrectomies and received intravenous bolus doses of MB-102 and meropenem. Once MB-102 equilibrated in the animal, CRRT was initiated. Continuous renal replacement therapy prescriptions comprised four combinations of blood pump (low versus high) and effluent (low versus high) flow rates. Changes in transdermal detected MB-102 clearance occurred immediately with a change in CRRT rates. Blood side meropenem clearance mirrored transdermal MB-102 clearance (r
2: 0.95–0.97, p value all <0.001). We suggest transdermal MB-102 clearance provides real-time personalized assessment of drug elimination and could optimize prescription of drugs for critically ill patients requiring CRRT.
Interaction of exercise and meal timing on blood glucose concentrations
Authors: Boulé Normand G. , Rees Jordan L.
Published: April 2023

Purpose of review

Exercise and diet are among the most studied behaviors that can affect blood glucose concentrations. Despite multiple studies examining these interventions in different populations and contexts, inconsistencies across studies have led to variable expectations. The purpose of this review is to more specifically examine how the timing of when exercise is performed in relation to meals can modify changes in glucose concentrations or insulin sensitivity. When possible, studies in type 2 diabetes are emphasized, but recent research in type 1 diabetes, obesity, and athletes is also considered.

Recent findings

The effect of a single bout of exercise performed after an overnight fast is often comparable to that of postprandial exercise on 24 h mean glucose concentrations. However, there is recent evidence to suggest that in some situations, but not all, longer term metabolic adaptations can be more favorable when exercise is regularly performed in the fasted state.

Exercise after an overnight fast can have different effects on glucose metabolism compared with postprandial exercise. The shorter term and longer term changes following fasting exercise can be relevant to those who are seeking greater glucoregulatory benefit from their exercise sessions, such as people with diabetes.
New approaches to diet therapy for eosinophilic esophagitis
Authors: Molina-Infante Javier , Mata-Romero Pilar , Martín-Holgado Daniel
Published: April 2023

Purpose of review

An empiric step-up (2–4–6) elimination diet remains the most common dietary approach in clinical practice when treating eosinophilic esophagitis (EoE). However, research in this field has fallen behind pharmacological therapy. This review aims to summarize novel approaches to dietary therapy for EoE.

Recent findings

A first prospective multicenter study in 41 pediatric patients (mean age 9 years) has evaluated the efficacy of a cow's milk elimination diet. This dietary approach led to histological remission in 51% of patients, albeit a caveat is that up to 80% of patients were receiving concomitant therapy with proton pump inhibitors. In a series of 18 adult patients with documented milk-induced EoE, ingestión of 400 ml of sterilized milk (boiled for up to 20 min) daily for 8 weeks did not induce histologic relapse in two-thirds of patients.

Milk elimination diet is effective in one-half of pediatric EoE patients and should likely be the first choice in children with EoE (within a step-up dietary approach). Promising data on tolerance of sterilized milk in adults with milk-induced EoE (66%) merit further replication in children, which may radically improve quality of life for patients and their caregivers.
A New Perspective on the Pathogenesis of Infantile Colic: Is Infantile Colic a Biorhythm Disorder?
Authors: Ucuncu Egeli Tugba , Tufekci Kemal Ugur , Ural Cemre , Durur Devrim Yagmur , Tuzun Erdogan Funda , Cavdar Zahide , Genc Sermin , Keskinoglu Pembe , Duman Nuray , Ozkan Hasan
Published: April 2023

Objectives:

In this study, we investigated the relationship between infantile colic, migraine, and biorhythm regulation, by evaluating biochemical and molecular parameters.

Study Design:

Healthy infants with and without infantile colic were eligible for this prospective cohort study. A questionnaire was applied. Between the 6th and 8th postnatal weeks, day and night circadian histone gene H3f3b mRNA expression and spot urine excretion of serotonin, cortisol, and 6-sulphatoxymelatonin were analyzed.

Results:

Among the 95 infants included, 49 were diagnosed with infantile colic. In the colic group, defecation difficulty, sensitivity to light/sound, and maternal migraine frequency increased and sleep disruption was typical. In the melatonin analysis, the difference between day and night levels was significant in the control group, indicating an established circadian rhythm (P = 0.014). In the colic group, there was no day-night difference (P = 0.216) in melatonin, but serotonin levels were higher at night. In the cortisol analysis, day-night values were similar in both groups. Day-night variability of H3f3b mRNA levels between the groups was significant, indicating circadian rhythm disturbance in the colic group compared to the control group (P = 0.003). Fluctuations in circadian genes and hormones expected in healthy rhythm were revealed in the control group, but were missing in the colic group.

Conclusion:

Due to the gaps in the etipathogenesis in infantile colic, a unique effective agent has not been discovered so far. This study, which demonstrated for the first time that infantile colic is a biorhythm disorder using molecular methods, fills the gap in this regard and points to a completely different perspective in terms of treatment.
Management Strategies for Geriatric Maxillofacial Fractures
Authors: Luo Guan-Jie , Chou Pang-Yun , Chen Chih-Hao
Published: April 2023

Background

Geriatric maxillofacial trauma has become an increasingly pressing clinical issue in Taiwan because of increased life expectancy.

Aim and Objectives

The purposes of this study were to investigate the anthropometric changes and the posttrauma outcomes in the aging population and to optimize the management strategies for geriatric facial fractures.

Materials and Methods

From 2015 to 2020, a total of 30 patients 65 years or older were identified to have suffered from maxillofacial fractures and presented at the emergency department of the Chang Gung Memorial Hospital (CGMH). These patients were categorized into group III, representing the elderly group. Two other groups (group I, age 18–40 years; group II, age 41–64 years) of patients were categorized based on their age. After applying propensity score matching to reduce bias caused by a large case number difference, patient demographics, anthropometric data, and management methods were compared and analyzed.

Results

Among 30 patients 65 years or older who met the inclusion criteria, the mean age of the matched group III was 77.31 ± 14.87 years, and the mean number of retained teeth was 11.77 (range, 3–20 teeth). The elderly patients had a significantly lower number of retained teeth (group I vs group II vs group III, 27.3 vs 25.23 vs 11.77; P < 0.001). Anthropometric data showed that facial bone structure degenerated significantly with advancing age. Outcome analysis demonstrated that falls accounted for 43.3% of injury mechanisms in the elderly group, followed by motorcycle accidents (30%) and car accidents (23.3%). Nineteen elderly patients (63%) received nonsurgical management. On the other hand, 86.7% of cases in the other 2 age groups underwent surgery. The average numbers of total hospital and intensive care unit stays in group III patients were 16.9 (range, 3–49 days) and 4.57 (range, 0–47 days), which was significantly longer than the other 2 age groups.

Conclusions

Our results suggested that not only surgery is feasible for elderly patients with facial fractures, but an acceptable result is often obtainable. However, an eventful course, including extended hospital/intensive care unit stays and an increased risk of associated injuries and complications, may be expected.
Characteristics of Hospitalized Adults 55 and Older With Clostridioides difficile Infection
Authors: Boone Anna W. , McCoy Thomas P. , Kennedy-Malone Laurie , Wallace Debra C. , Yasin Reham
Published: April 2023

Clostridioides difficile infection in older adults can result in severe infection, difficulty in treating, and complicated disease process, yet few studies have examined the characteristics of hospitalized older adults and recurrent Clostridioides difficile infection. A retrospective cohort study was conducted to explore the characteristics of hospitalized adults 55 years and older with initial Clostridioides difficile infection and recurrences by extracting routinely documented data in the electronic health record. A sample of 1,199 admissions on 871 patients was included, with a recurrence rate of 23.9% (n = 208). During the first admission, there were 79 deaths (9.1%). Clostridioides difficile infection recurrence was more prevalent in patients between 55 and 64 years old, and if discharged to a skilled nursing facility or with home health services. Chronic diseases significantly more prevalent in recurrent Clostridioides difficile infection included hypertension, heart failure, and chronic kidney disease. On initial admission, no laboratory abnormalities were significantly associated with recurrent Clostridioides difficile infection. This study indicates the need for utilizing routinely captured electronic health record data during acute hospitalizations to aid in targeting care to reduce morbidity, mortality, and recurrence.
Leslie Lars Iversen. 31 October 1937—30 July 2020
Authors: Robbins FRS Trevor W.
Published: April 2023

Leslie Iversen was one of the most distinguished UK neuropharmacologists and neuroscientists. He led basic neuroscience research at Cambridge early in his career, in partnership with his wife Susan D. Iversen, directing the influential MRC Neurochemical Pharmacology Unit, which spawned a remarkable generation of outstanding neuroscientists. He subsequently made what was then an unusual transition to the industrial sector, to lead a major new research unit of Merck, Sharp and Dohme at Harlow, taking up the difficult challenge of discovering new compounds to transform psychiatry and neurology. Throughout his career he made seminal contributions to the study of the chemical neurotransmitters of the brain, and thereby to the mechanisms of action of drugs now commonly used in psychiatry such as the so-called anti-depressants and the anti-psychotics. His early work focused on the catecholamines (noradrenaline and dopamine) and subsequently the amino acids (gamma aminobutyric acid and glutamate), later extending to an entirely new class of transmitters, the neuropeptides. This work also helped to redefine the very concept of ‘neurotransmitter’. Late in his career he chaired the important Advisory Council on the Misuse of Drugs, as a veritable but discreet ‘Drug Tsar’, and contributed a number of scholarly monographs as a visiting professor at Oxford.
Streptomyces salinarius sp. nov., an actinomycete isolated from solar saltern soil
Authors: Klanbut Khanungkan , Rattanakavil Thitiya , Duangupama Thitikorn , Suriyachadkun Chanwit , Herron Paul Robert , Thawai Chitti
Published: April 2023

An actinobacterium, designated strain SS06011T, was isolated from solar saltern soil collected from Samut Sakhon province, Thailand. The taxonomic position of this strain was established using the polyphasic taxonomic approach. The strain produced grey aerial spore mass on International

Streptomyces

Project 2 seawater agar that differentiated into spiral spore chains with rugose-surfaced spores. Strain SS06011T was found to have
ll
-diaminopimelic acid in the cell peptidoglycan. Whole-cell hydrolysates contained galactose, glucose and ribose. MK-9(H6) and MK-9(H4) were major menaquinones. The major cellular fatty acids comprised iso-C16 : 0, anteiso-C15 : 0 and anteiso-C17 : 0. Diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol and phosphatidylinositol were detected in cells. These characteristics were coincident with the typical morphological and chemotaxonomic properties of the genus

Streptomyces

. The taxonomic affiliation at the genus level of this strain could also be confirmed by its 16S rRNA gene sequence data. Strain SS06011T showed the highest 16S rRNA gene sequence similarity to

Streptomyces ardesiacus

NRRL B-1773T (99.1 %),

Streptomyces coelicoflavus

NBRC 15399T (99.1 %) and

Streptomyces hyderabadensis

OU-40T (99.1 %). Digital DNA–DNA hybridization (dDDH), average nucleotide identity-blast (ANIb) and average amino acid identity (AAI) values between strain SS06011T and its closely related type strains,

S. ardesiacus

NBRC 15402T,

S. coelicoflavus

NBRC 15399T and

S. hyderabadensis

JCM 17657T, were in the range of 45.4–48.4 % (for dDDH), 90.8–91.9 % (for ANIb) and 90.8–91.7 % (for AAI), respectively, which are lower than the cut-off criteria for species delineation. The DNA G+C content of genomic DNA was 71.9 mol%. With the differences in physiological, biochemical and genotypic data, strain SS06011T could be discriminated from its closest neighbours. Thus, strain SS06011T should be recognized as representing a novel species of the genus

Streptomyces

, for which the name Streptomyces salinarius sp. nov. is proposed. The type strain is SS06011T (=TBRC 9951T=NBRC 113998T).
The change of inflammatory status and vaginal flora in pregnant women with premature rupture of membranes
Authors: Gai Shukun , Wu Qian , Zhang Huijie
Published: April 2023

Introduction. Premature rupture of the membrane (PROM) can trigger significant maternal complications, even maternal and fetal morbidity or mortality.

Hypothesis. Inflammatory status and vaginal flora might be utilized to predict the occurrence of PROM.

Aim. To explore the association between the occurrence of PROM and vaginal flora and inflammatory status alteration.

Methodology. A case-control cross-sectional study was carried out on 140 pregnant women with or without PROM. Socio-demographic characteristics, vaginal flora assessment, pregnant outcomes and Apgar score information were retrieved.

Results. Pregnant women with PROM showed an increased incidence of vulvovaginal candidiasis (VVC), trichomonas vaginitis (TV) and bacterial vaginitis (BV) with dysregulated vaginal flora and diminished fetal tolerance of labour indicated by down-regulated Apgar score. The increased rate of prematurity, puerperal infection and neonatal infection could be detected in PROM patients with imbalanced vaginal flora compared with PROM patients with normal vaginal flora. ROC analysis suggested IL-6 and TNF-α yielded the best discrimination for the prediction of PROM.

Conclusion. Altered vaginal and inflammatory status are associated with PROM, and IL-6 and TNF-α can predict the occurrence of PROM.
Congenital Heart Disease: Assessing Viral Etiology in infants attending at a tertiary care hospital
Authors: Mehreen Syeda Fakiha , Srinath Mote , Sultana Waseema , Rani Vannavada Sudha
Published: April 2023

Background

Congenital heart disease (CHD) is the commonest birth defect worldwide, affecting millions of newborns every year. Limited information is available regarding risk factors for its causation.

Objectives

This study was planned with an aim to determine the viral etiology in infants with congenital heart disease. Although a number of viruses diseases have been etiologically linked to congenital defects, only two viruses namely rubella virus and cytomegalovirus are definitely proved to be associated with anomalies in infants.

Materials and Methods

This Prospective study was conducted at a paediatric tertiary care hospital for a period of 6 months. Hundred (100) Infants with structural Congenital heart defects (CHD) based on Echocardiography findings were included in the study after taking informed consent from their mothers. Serum samples were collected and sent to Virology lab. The samples were tested for Rubella and Cytomegalovirus IgM antibodies using Enzyme Linked Immunosorbent Assay (ELISA).

Results

Out of 100 infants with congenital heart defects, (M: F:56:44) 4% were seropositive for rubella IgM antibodies whereas 20% showed seropositivity of Cytomegalovirus IgM antibodies. Median age of infants was 25 days. The most common congenital heart defect in Rubella positive infants was Patent ductus arteriosus followed by Atrial septal defect whereas it was Patent ductus arteriosus only in CMV positive infants followed by Patent Foramen ovale. 6% of infants died and among them 50% had infection with CMV while 11% showed infection with Rubella.

Conclusion

Regular screening by TORCH (Toxoplasmosis, Rubella, Cytomegalovirus, HSV) panel testing of mothers in first trimester is necessary for early detection. Early vaccination strategies should be implemented. Rapid and correct diagnosis of congenital CMV and Rubella infections in infants is very important for the correct therapy selection and proper management of the cases.
Florida Doulas’ Perspectives on their Role in Reducing Maternal Morbidity and Health Disparities
Authors: Applequist Janelle , Wilson Roneé , Perkins Megan , Williams Charlette , Joglekar Ria , Powis Richard , Daniel Angela , Louis-Jacques Adetola F.
Published: April 2023

Introduction

Maternal mortality rates continue to rise in the United States. Considerable racial disparities exist, as Black women are 2-3 times more likely to die from pregnancy-related complications than White women. Doulas have been associated with improved maternal outcomes. This study aimed to 1) investigate Florida doulas’ perspectives on severe maternal morbidity/mortality, related inequities, and their influence on these areas as well as 2) identify opportunities for actionable change.

Methods

This qualitative study included seven online, in-depth interviews and seven focus groups with doulas (n= 31) in the state of Florida. Interview and focus group guides aimed to investigate how doulas perceive their role in the context of a) maternal morbidity and b) health disparities/inequities.

Results

Doulas associated maternal morbidity and health disparities with Black pregnant people, attributing racism as a major contributor. Doulas identified their role in mitigating this problem as one that involves: providing positive social surveillance and emotional support, equipping clients with access to education and resources, and championing for advocacy in healthcare settings. Actionable steps utilizing the social ecological model and reproductive justice framework are provided.

Discussion and Health Equity Implications

Doulas perceived their role as integral to mitigating maternal morbidity and maternal health disparities, particularly in the context of race. Equitable access to doulas for low-income and or minoritized populations may be one key strategy to improve maternal health equity.
Risk Factors for Adverse Outcomes with Outpatient Parenteral Antimicrobial Therapy
Authors: Wang Alexander J. , Elnakieb Yaser , Bae Esther , Monogue Marguerite , Cutrell James B. , Lehmann Christoph U. , Yen Christina , Medford Richard J.
Published: April 2023

Objectives

Outpatient parenteral antimicrobial therapy (OPAT) use has increased significantly as it provides safe and reliable administration of long-term antimicrobials for severe infections. Benefits of OPAT include fewer antibiotic or line-related complications, increased patient satisfaction, shorter hospitalizations, and lower costs. Although OPAT programs carefully screen patients for eligibility and safety prior to enrollment, complications can occur. There is a paucity of studies identifying predictors of clinical outcomes in OPAT patients. Here, we seek to identify baseline predictors of OPAT outcomes utilizing machine learning methodologies.

Methods

We used electronic health record data from patients treated with OPAT between February 2019 and June 2022 at a large academic tertiary care hospital in Dallas, Texas. Three primary outcomes were examined: 1) clinical improvement at 30 days without evidence of reinfection; 2) patient actively being followed at 30 days; and 3) occurrence of any adverse event while on OPAT. Potential predictors were determineda priori, including demographic and clinical characteristics, OPAT setting, intravenous line type, and antimicrobials administered. Three classifiers were used to predict each outcome: logistic regression, random forest, and extreme gradient boosting (XGBoost). Model performance was measured using AUC, F1, and accuracy scores.

Results

We included 664 unique patients in the study, of whom 57% were male. At 30 days, clinical improvement was present in 78% of patients. Two-thirds of patients (67%) were actively followed at 30 days, and 30% experienced an adverse event while on OPAT. The XGBoost model performed best for predicting treatment success (average AUC = 0.873), with significant predictors including ID consultation and the use of vancomycin. The logistic regression model was best for predicting adverse outcomes (average AUC = 0.710). Risk factors for adverse outcomes included management in the home setting and the use of vancomycin, daptomycin, or piperacillin-tazobactam.

Conclusion

Outcomes of patients undergoing OPAT can be predicted with the use of easily-obtainable clinical and demographic factors. Patients requiring certain antimicrobial therapies, such as vancomycin or daptomycin, may derive less benefit from early hospital discharge and OPAT.
Enhanced Classification Performance using Deep Learning Based Segmentation for Pulmonary Embolism Detection in CT Angiography
Authors: Kahraman Ali Teymur , Fröding Tomas , Toumpanakis Dimitris , Gustafsson Christian Jamtheim , Sjöblom Tobias
Published: April 2023

Purpose

To develop a deep learning-based algorithm that automatically and accurately classifies patients as either having pulmonary emboli or not in CT pulmonary angiography (CTPA) examinations.

Materials and Methods

For model development, 700 CTPA examinations from 652 patients performed at a single institution were used, of which 149 examinations contained 1497 PE traced by radiologists. The nnU-Net deep learning-based segmentation framework was trained using 5-fold cross-validation. To enhance classification, we applied logical rules based on PE volume and probability thresholds. External model evaluation was performed in 770 and 34 CTPAs from two independent datasets.

Results

A total of 1483 CTPA examinations were evaluated. In internal cross-validation and test set, the trained model correctly classified 123 of 128 examinations as positive for PE (sensitivity 96.1%; 95% C.I. 91-98%;P< .05) and 521 of 551 as negative (specificity 94.6%; 95% C.I. 92-96%;P< .05). In the first external test dataset, the trained model correctly classified 31 of 32 examinations as positive (sensitivity 96.9%; 95% C.I. 84-99%;P< .05) and 2 of 2 as negative (specificity 100%; 95% C.I. 34-100%;P< .05). In the second external test dataset, the trained model correctly classified 379 of 385 examinations as positive (sensitivity 98.4%; 95% C.I. 97-99%;P< .05) and 346 of 385 as negative (specificity 89.9%; 95% C.I. 86-93%;P< .05).

Conclusion

Our automatic pipeline achieved beyond state-of-the-art diagnostic performance of PE in CTPA using nnU-Net for segmentation and volume- and probability-based post-processing for classification.

Highlights

An nnU-Net segmentation framework was applied to patient-level classification in CTPA examinations.

The proposed algorithm can enable prioritization of patients with PE for rapid review in emergency radiology.

The proposed algorithm showed outstanding performance on both internal and two publicly available external testing datasets (AUC, 98.3%; n=1355).
Epidemiology of scrub typhus and other rickettsial infections (2018-22) in the hyper-endemic setting of Mizoram, North-East India
Authors: Vanramliana  , Pautu Lalfakzuala , Lalmalsawma Pachuau , Rosangkima Gabriel , Sarma Devojit Kumar , Hunropuia  , Malvi Yogesh , Kodali Naveen Kumar , Amarthaluri Christiana , Balasubramani K , Nina Praveen Balabaskaran
Published: April 2023

In the last decade, there has been an emergence of scrub typhus in many parts of India. In Mizoram, North-East India, there has been a steep increase in scrub typhus and other rickettsial infections in the last 5 years. As part of the public health response, the Mizoram Government has integrated screening (by rapid immunochromatographic test and/or Weil-Felix test) and line listing of scrub typhus and other rickettsial infections across all its health settings, a first in India. From 2018-22 (study period), 22914 cases were reported; of these, 19651 were positive for scrub typhus. Aizawl district is the worst affected, with 10580 cases (46.17%). The average incidence rate of rickettsial infections is 3.54 cases per 1000 persons-year, and the case fatality rate is 0.35. Patients with eschar (aOR=2.5, p<0.05), construction workers (aOR=17.9, p<0.05), and children aged 10 and below (aOR=5.4, p<0.05) have higher odds of death due to rickettsial infections.
Keystone competitor creates spatial patterns of biodiversity
Authors: Ennis Katherine K. , Perfecto Ivette , Vandermeer John
Published: April 2023

Conventional ecological theory on competition and competitive exclusion states that competition should limit diversity. However, diversity of all species is more common than competitive exclusion would suggest, especially in the tropics. Here, we use theoretical and field approaches to examine the relationship between a keystone ant competitor (Azteca sericeasur) and the richness of a ground-foraging ant community in a spatially explicit context. Theoretically, we demonstrate that a fixed keystone competitor can increase species diversity. In addition, we sampled the ground-foraging ant community in three differentially managed coffee habitats and found – with the exception of plots in the most intensified coffee habitat – a consistently higher species richness near to the keystone competitor and lower richness with increasing distance. These patterns show that keystone competitors may contribute to the maintenance of local species richness.
hipFG: High-throughput harmonization and integration pipeline for functional genomics data
Authors: Cifello Jeffrey , Kuksa Pavel P. , Saravanan Naveensri , Valladares Otto , Leung Yuk Yee , Wang Li-San
Published: April 2023

Preparing functional genomic (FG) data with diverse assay types and file formats for integration into analysis workflows that interpret genome-wide association and other studies is a significant and time-consuming challenge. Here we introduce hipFG, an automatically customized pipeline for efficient and scalable normalization of heterogenous FG data collections into standardized, indexed, rapidly searchable analysis-ready datasets while accounting for FG datatypes (e.g., chromatin interactions, genomic intervals, quantitative trait loci).

Availability and Implementation

hipFG is freely available athttps://bitbucket.org/wanglab-upenn/hipFG. Docker container is available athttps://hub.docker.com/r/wanglab/hipfg.

Contact

lswang@pennmedicine.upenn.edu

Supplementary information

Supplementary data are available as BioRxiv supplemental files.
Representation Learning to Effectively Integrate and Interpret Omics Data
Authors: Masarone Sara
Published: April 2023

The last decade has seen an increase in the amount of high throughput data available to researchers. While this has allowed scientists to explore various hypotheses and research questions, it has also highlighted the importance of data integration to facilitate knowledge extraction and discovery. Although many strategies have been developed over the last few years, integrating data whilst generating an interpretable embedding still remains challenging due to difficulty in regularisation, especially when using deep generative models. Thus, we introduce a framework called Regularised Multi-View Variational Autoencoder (RMV-VAE) to integrate different omics data types whilst allowing researchers to obtain more biologically meaningful embeddings.
Combined inactivation of RB and Hippo pathways converts differentiating photoreceptors into eye progenitor cells through derepression ofhomothorax
Authors: Rader Alexandra E. , Bayarmagnai Battuya , Frolov Maxim V.
Published: April 2023

The RB and Hippo pathways interact to regulate cell proliferation and differentiation. However, their mechanism of interaction is not fully understood.Drosophilaphotoreceptors with inactivated RB and Hippo pathways specify normally but fail to maintain neuronal identity and dedifferentiate. We performed single-cell RNA-sequencing to elucidate the cause of dedifferentiation and the fate of these cells. We find that dedifferentiated cells adopt a progenitor-like fate due to inappropriate activation of the retinal differentiation suppressorhomothorax(hth) by Yki/Sd. This results in activation of the Yki/Hth transcriptional program, driving photoreceptor dedifferentiation. We show that Rbf physically interacts with Yki which, together with the GAGA factor, inhibitshthexpression. Thus, RB and Hippo pathways cooperate to maintain photoreceptor differentiation by preventing inappropriate expression ofhthin differentiating photoreceptors. Our work accentuates the importance of both RB and Hippo pathway activity for maintaining the state of terminal differentiation.
Stem cell growth directs region-specific cell fate decisions during intestinal nutrient adaptation
Authors: Mattila Jaakko , Viitanen Arto , Fabris Gaia , Korzelius Jerome , Hietakangas Ville
Published: April 2023

The adult intestine is a regionalized organ, whose size and cellular composition is adjusted in response to nutrient status. This involves dynamic regulation of intestinal stem cell (ISC) proliferation and differentiation. How nutrient signaling controls cell fate decisions to drive regional changes in cell type composition remains unclear. Here we show that nutrient adaptation involves region-specific control of intestinal cell size, number and differentiation. We uncovered that activation of mTOR complex 1 increases ISC size in a region-specific manner. This promotes Delta expression to direct cell fate towards the absorptive enteroblast lineage, while inhibiting secretory enteroendocrine cell differentiation. The observed coupling between nutrient sensing and cell fate enabled mitigation of aging-induced ISC misdifferentiation through intermittent fasting. In conclusion, ISC size acts as an early fate determinant allowing regional control of intestinal cell differentiation in response to nutrition with relevance to maintenance of tissue integrity during aging.

Highlights

mTORC1 signaling regulates ISC size in a region-specific manner

mTORC1 signaling is activated in the S and G2 phase of the ISC cell cycle

ISC size directs differentiation towards absorptive vs. secretory lineage

Intermittent fasting mitigates aging induced deregulation of ISC differentiation

GRAPHICAL ABSTRACT
Determining The Structure of the Bacterial Voltage-gated Sodium Channel NaChBac Embedded in Liposomes by Cryo Electron Tomography and Subtomogram Averaging
Authors: Chang Shih-Ying Scott , Dijkman Patricia M. , Wiessing Simon A. , Kudryashev Misha
Published: April 2023

Voltage-gated sodium channels shape action potentials that propagate signals along cells. When the membrane potential reaches a certain threshold, the channels open and allow sodium ions to flow through the membrane depolarizing it, followed by the deactivation of the channels. Opening and closing of the channels is important for cellular signalling and regulates various physiological processes in muscles, heart and brain. Mechanistic insights into the voltage-gated channels are difficult to achieve as the proteins are typically extracted from membranes for structural analysis which results in the loss of the transmembrane potential. Here, we report the structural analysis of a bacterial voltage-gated sodium channel, NaChBac, reconstituted in liposomes under an electrochemical gradient by cryo electron tomography and subtomogram averaging. We show that the small channel, most of the residues of which are embedded in a membrane, can be localized using a genetically fused GFP. GFP can aid the initial alignment to an average resulting in a correct structure, but does not help for the final refinement. At a moderate resolution of ∼16 Å the structure of NaChBac in an unrestricted membrane bilayer is 10% wider than the structure of a purified protein previously solved in nanodiscs, suggesting the potential movement of the peripheral voltage-sensing domains. Our structural analysis explores the limits of structural analysis of membrane proteins in membranes.

HIGHLIGHTS

Structural analysis of the bacterial voltage-gated sodium channel NaChBac in lipid vesicles under the resting membrane potential by cryo electron tomography and subtomogram averaging.

Fused GFP allows identification of a 120-kDa mostly transmembrane protein in tomograms, and helps for the initial alignment but not for the final refinements.

The map of NaChBac in liposomes at a resolution of 16.3 Å is ∼10% wider than the protein structure in a nanodisc.
Class I histone deacetylase complex: structure and functional correlates
Authors: Wang Xiao , Wang Yannan , Liu Simiao , Zhang Yi , Xu Ke , Ji Liting , Kornberg Roger D. , Zhang Heqiao
Published: April 2023

Schizosaccharomyces pombeClr6S, a class I histone deacetylase complex, functions as a zinc-dependent enzyme to remove acetyl groups from lysine residues in histone tails. We report here the cryo-EM structures of Clr6S alone and in a complex with a nucleosome. The active center, revealed at near atomic resolution, includes features important for catalysis - a water molecule coordinated by zinc, the likely nucleophile for attack on the acetyl-lysine bond, and a loop that may position the substrate for catalysis. The cryo-EM map in the presence of a nucleosome reveals multiple Clr6S-nucleosome contacts, and a high degree of relative motion of Clr6S and the nucleosome. Such flexibility may be attributed to interaction at a site in the flexible histone tail, and is likely important for function of the deacetylase, which acts at multiple sites in other histone tails.
c-di-AMP determines the hierarchical organization of bacterial RCK proteins
Authors: Rocha Rita , Jorge João M. P. , Texeira-Duarte Celso M. , Figueiredo-Costa Inês R. , Herzberg Christina , Stülke Jörg , Morais-Cabral João H.
Published: April 2023

RCK domains or proteins are important regulatory components of cation and K+channels and transporters both in eukaryotic and prokaryotic organisms. A lasting unanswered question about bacterial RCK proteins relates to the physiological role of the multiple, sometimes closely related, RCK genes encoded in the genome. We explored this question with the Ktr channels ofBacillus subtilisthat include two genes encoding RCK proteins (KtrA and KtrC) and two genes encoding their membrane protein partners (KtrB and KtrD). Using a combination ofin vivocharacterization andin vitrofunctional analysis, we determined that the two RCK proteins are neither physiologically redundant or functionally equivalent. Instead, KtrC is the physiologically dominant RCK protein due to its ability to mediate K+transport inactivation by c-di-AMP, a bacterial second messenger that is the master regulator of the K+machinery in many species, while KtrA assembled channels are very insensitive to the dinucleotide. Moreover, KtrC and KtrA can form heteromeric assemblies that can control the Ktr channel activity and are sensitive to c-di-AMP inhibition. In parallel, we showed that conditions with a large number of Ktr channels assembled with KtrA, or with RCK proteins that do not mediate c-di-AMP inhibition, are toxic to the cell. Altogether, we have demonstrated that c-di-AMP regulation of Ktr channels goes beyond affecting transcription and functional activity, it also determines the hierarchical organization of bacterial RCK proteins.