bluuebunny/crossref_metadata_2025 huggingface dataset:
Construction of and Conversion to Continent Ileostomy: A Systematic Review
Authors: Angistriotis Athanasios , Shen Bo , Kiran Ravi Pokala
Published: September 2022

BACKGROUND:

Continent ileostomy was first introduced by Nils Kock in 1969 as Kock pouch (K pouch). Its most characteristic feature, the nipple valve that offers continence was a later addition. Even though today's continent ileostomy is sidelined by ileal-pouch anal anastomosis as the gold standard of restorative procedures for colectomy patients, it remains an excellent option for select patients, offering an alternative to end-ileostomy or a poorly functioning ileoanal pouch.

OBJECTIVE:

This study aims to summarize principles and techniques behind Kock pouch construction, both de novo and as “J to K” conversion, as well as examine surgical outcomes following the procedure in the modern era regardless of indication.

DATA SOURCES:

Data sources included Pubmed and Cochrane Library up to July 2021.

STUDY SELECTION:

Articles reviewing continent ileostomy procedures and outcomes between 2000 and 2021. Case reports and series <15 were excluded.

RESULTS:

Fifteen articles were selected for review describing 958 patients with a Kock continent ileostomy, 510 patients who had undergone a Barnett continent intestinal reservoir, and 40 that had undergone construction of a T-pouch.

CONCLUSION:

Continent ileostomies carried out in specialized centers by experienced surgeons can be a great option for patients who would otherwise be confined by an end ileostomy. High pouch survival rates with higher quality-of-life scores than end ileostomy and comparable to ileal pouch-anal anastomosis, make continent ileostomy a great option, even if we take into account the less than ideal reoperation and complication rates. It is, however, of paramount importance that patients are carefully selected, thoroughly educated, highly motivated, and engaged in their care. Specifically, for patients with Crohn’s disease, further research is needed to help elucidate factors that affect pouch survival and candidacy for Kock pouch creation. Lastly, continuous surgical technique modifications and refinements can allow even more patients to be considered suitable for the procedure.
Validation of ICD-10-CM Diagnosis Codes for Gestational Age at Birth
Authors: Leonard Stephanie A. , Panelli Danielle M. , Gould Jeffrey B. , Gemmill Alison , Main Elliott K.
Published: September 2022

Background:

The International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) introduced diagnosis codes for week of gestation. Our objective was to assess the validity of these codes among live births, which could have major utility in perinatal research and quality improvement.

Methods:

We used linked birth certificate and patient discharge data from births in California during 2016–2019 (N = 1,843,992). We identified gestational age using Z3A.xx ICD-10-CM diagnosis codes in birthing patient discharge data and compared it with the gold standard of obstetric estimate, as recorded on the birth certificate. We further assessed sensitivity and specificity of gestational age categories (≥37 weeks, <37 weeks, <32 weeks, <28 weeks), given these categories are frequently of interest, and evaluated differences in validity of preterm birth (<37 weeks’ gestation) by patient characteristics.

Results:

One-million seven-hundred seventy-thousand one-hundred three patients had a gestational age recorded in patient discharge and birth certificate data. When comparing gestational age in patient discharge data with birth certificate data, the concordance correlation coefficient was 0.96 (95% confidence interval [CI] = 0.96, 0.96) and the mean difference between the two measurements was 0.047 weeks (95% CI = 0.046, 0.047 weeks). Ninety-five percent of the differences between the two measurements were between –1.00 week and +1.09 weeks. Sensitivity and specificity were 0.94 to 1.00 for all gestational age categories and were 0.94 to 1.00 for preterm birth across sociodemographic groups.

Conclusions:

We found week-specific gestational age at delivery ICD-10-CM diagnosis codes in patient discharge data to have high validity when compared with the best obstetric estimate on the birth certificate.
The effects of citalopram, SB-334867 and orexin-1, alone or in various combinations, on the anxiogenic-like effects of REM sleep deprivation in male mice
Authors: Saadati Naghmeh , Bananej Maryam , Khakpai Fatemeh , Zarrindast Mohammad-Reza , Alibeik Hengameh
Published: September 2022

Sleep deprivation may induce anxiety. On the other hand, anxiety disorders elicit main changes in the quality of sleep. Moreover, orexin and citalopram play a role in the modulation of insomnia and mood diseases. Thus, we planned preclinical research to evaluate the effect of combinations of orexin agents and citalopram on anxiety behavior in rapid eye movement (REM) sleep-deprived mice. For drug intracerebroventricular (i.c.v.) infusion, the guide cannula was surgically implanted in the left lateral ventricle of mice. REM sleep deprivation was conducted via water tank apparatus for 24 h. The anxiety behavior of mice was evaluated using the elevated plus maze (EPM). Our results revealed that REM sleep deprivation reduced the percentage of open arm time (%OAT) and the percentage of the open arm entries (%OAE) but not closed arm entries (locomotor activity) in the EPM test, presenting an anxiogenic response (P < 0.05). We found a sub-threshold dose of SB-334867, orexin-1 receptor antagonist, and orexin-1 which did not alter anxiety reaction in the REM sleep-deprived mice (P > 0.05). Intraperitoneal (i.p.) injections of citalopram (5 and 10 mg/kg) increased both %OAT and %OAE (P < 0.001) representing an anxiolytic effect, but not locomotor activity in the REM sleep-deprived mice. Interestingly, co-treatment of citalopram (1, 5 and 10 mg/kg; i.p.) and SB-334867 (0.1 µg/mouse; i.c.v.) potentiated the anxiolytic effect in the REM sleep-deprived mice. On the other hand, co-treatment of different dosages of citalopram along with a sub-threshold dose of orexin-1 did not alter %OAT, %OAE, and locomotor activity in the REM sleep-deprived mice. We found a synergistic anxiolytic effect of citalopram and SB-334867 in the REM sleep-deprived mice. These results suggested an interaction between citalopram and SB-334867 to prevent anxiogenic behavior in the REM sleep-deprived mice.
Silencing of Long Noncoding RNA TUG1 Ameliorates Atherosclerosis-Induced Myocardial Injury by Upregulating microRNA-30b-3p and Downregulating Brd4
Authors: Li De-long , Zheng Bin-bin , Zeng Xin , Li Jiahua , Dai Ruo-zhu
Published: September 2022

Long noncoding RNAs and microRNAs (miRNAs) are emerging biomarkers involved in human diseases, and we focused on the roles of long noncoding RNA taurine upregulated gene 1 (TUG1) and miR-30b-3p in the related mechanisms of atherosclerosis-induced myocardial injury. ApoE-deficient mice were fed with high-fat diet to establish atherosclerotic models and then were subjected to either TUG1 downregulation or miR-30b-3p upregulation treatment. The serum myocardial enzymes, inflammatory biomarkers, pathological changes, intramyocardial macrophage infiltration, and apoptosis of cardiomyocytes in atherosclerotic mice were determined. The expression of TUG1, miR-30b-3p, and bromodomain protein 4 (Brd4) in atherosclerotic models was evaluated. Moreover, the correlations of TUG1, miR-30b-3p, and Brd4 were verified. TUG1 and Brd4 were increased while miR-30b-3p was decreased in atherosclerotic mice. The silenced TUG1 or elevated miR-30b-3p attenuated atherosclerosis-induced myocardial injury mainly by reducing serum myocardial enzyme content and inflammatory response, improving pathological changes, and preventing macrophage infiltration and cardiomyocyte apoptosis in atherosclerotic mice. Mechanistically, TUG1 could competitively bind with miR-30b-3p to prevent the degradation of its target gene Brd4. This study reveals that the silencing of TUG1 ameliorates atherosclerosis-induced myocardial injury by upregulating miR-30b-3p and downregulating Brd4, which may provide novel targets for atherosclerosis treatment.
A Cross-Sectional Descriptive Analysis of Diversity, Equity, and Inclusion Presence Among United States Occupational and Environmental Medicine Residency Program Websites
Authors: Chaudhry Zaira S. , Widarma Crystal , Cadet Leslie , Das Rupali , Sharip Akbar
Published: September 2022

Objective

To evaluate the presence of diversity, equity, and inclusion (DEI) among US occupational and environmental medicine (OEM) residency program websites.

Methods

In January to February 2022, two independent reviewers evaluated the websites of all 24 US accredited OEM residency programs and documented the presence of 10 predetermined DEI metrics and resident/faculty photographs and biographies.

Results

Program websites included a median of 1 (0–3) DEI element with 46% of websites containing none of the DEI metrics. Faculty photographs and biographies were included in 83% and 75% of websites, respectively. Resident photographs and biographies were included in 50% and 25% of websites, respectively.

Conclusions

Many OEM residency program websites lack DEI presence. Programs should consider presenting information relevant to DEI on their websites to help attract more diverse applicant pools.
Substance use disorders in organ transplantation: perennial challenges and interprofessional opportunities
Authors: Winder Gerald S. , Clifton Erin G. , Mellinger Jessica L.
Published: September 2022

Purpose of review

The current article examines recent publications regarding ongoing clinical and ethical challenges and opportunities related to substance use disorders (SUD) in solid organ transplantation (SOT) utilizing a lens of interprofessional clinical models and care delivery.

Recent findings

Innovative interprofessional clinician skillsets and care models are increasingly emphasized in the SOT literature as the standard of care for common, complex psychosocial problems like substance use and SUD. Cannabinoids are common among candidates and recipients and present several unique quandaries to SOT teams. Opioid use disorder treatment can often be definitively treated with medications that SOT teams may find unfamiliar, controversial, or aversive. Arguably the quintessential example of SUD in SOT, early liver transplantation for patients with alcohol-related liver disease and short periods of sobriety has become increasingly common and accepted in recent years requiring liver teams to rapidly acquire significant interprofessional psychiatric awareness and expertise. The question of retransplantation in patients who have experienced recurrent SUD remains unsettled.

Regardless of substances used or organs transplanted, interprofessional care continues to emerge as a foundational aspect of clinical care and research in SOT.
Brief Report: Performance of Tuberculosis Symptom Screening Among Hospitalized ART-Naive Children With HIV in Kenya
Authors: Cranmer Lisa M. , Njuguna Irene N. , LaCourse Sylvia M. , Figueroa Janet , Gillespie Scott , Maleche-Obimbo Elizabeth , Otieno Vincent , Mugo Cyrus , Okinyi Helen , Benki-Nugent Sarah , Pavlinac Patricia B. , Malik Amyn A. , Gandhi Neel R. , Richardson Barbara A. , Stern Joshua , Wamalwa Dalton C. , John-Stewart Grace C.
Published: September 2022

Background:

The World Health Organization (WHO) recommends tuberculosis (TB) diagnostic evaluation for children with HIV (CHIV) who have history of TB contact, poor weight gain, cough, or fever. These screening criteria were developed based on studies of symptomatic CHIV with incomplete microbiologic confirmation. We performed routine TB microbiologic evaluation of hospitalized CHIV with and without symptoms to develop a data-driven TB symptom screen.

Methods:

Among hospitalized antiretroviral therapy–naive Kenyan CHIV enrolled in the Pediatric Urgent Start of Highly Active Antiretroviral Therapy (PUSH) trial, we performed Xpert MTB/RIF and mycobacterial culture of respiratory and stool specimens independent of TB symptoms. We evaluated performance of WHO and other published pediatric TB screening criteria and derived optimized criteria using a combination of symptoms.

Results:

Of 168 CHIV who underwent TB microbiologic evaluation, 13 (8%) had confirmed TB. WHO TB symptom screening had 100% sensitivity and 4% specificity to detect confirmed TB. Published TB screening criteria that relied on prolonged symptoms missed cases of confirmed TB (sensitivity 85%–92%). An optimized symptom screen including weight loss, cough, anorexia, or TB contact had 100% sensitivity and improved specificity (31%) compared with the WHO pediatric TB symptom screen.

Conclusions:

The WHO TB symptom screen was highly sensitive but resulted in a high proportion of hospitalized CHIV who would require TB diagnostic evaluation. Other published TB screening criteria missed CHIV with confirmed TB. Our optimized screening tool increased specificity while preserving sensitivity. Future multicenter studies are needed to improve TB screening tools for CHIV in both inpatient and outpatient settings.
Time-of-Flight Angiography in Ultra-High-Field 7 T MRI for the Evaluation of Peroneal Perforator Arteries Before Osseomyocutaneous Flap Surgery
Authors: Wiesmueller Marco , Meixner Christian R. , Weber Manuel , Kesting Marco , Nagel Armin M. , Wuest Wolfgang , May Matthias S. , Roemer Frank W. , Uder Michael , Heiss Rafael
Published: September 2022

Objectives

Presurgical identification and morphologic characterization of the peroneal perforator arteries (PPAs) are essential for osseomyocutaneous flap surgery. The aim of this study was to evaluate PPAs using time-of-flight (TOF) angiography in 7 T magnetic resonance imaging in comparison with dual-energy computed tomographic angiography (CTA).

Materials and Methods

In this prospective study, TOF angiography and CTA of both lower legs were acquired before flap surgery from 07/2019 to 02/2020. Magnetic resonance imaging was performed using a dedicated 28-channel knee coil with an acquisition time of 9:55 minutes (voxel size: 0.4 × 0.4 × 0.8 mm). Computed tomographic angiography was acquired with a third-generation dual-source computed tomography on the same day. Virtual monoenergetic reconstructions at 40 keV photon energy served as the standard of reference for PPA identification and subtyping. Two independent readers assessed the image quality, quantity, length assessment, and classification according to surgical considerations of PPAs for TOF angiography and CTA. Both TOF angiography and CTA were used for presurgical flap design and were evaluated by an orofacial surgeon.

Results

Ten patients (mean age, 59.9 ± 14.9 years; 7 men) were included. Time-of-flight angiography and CTA identified 53 and 51 PPAs in total, respectively. Time-of-flight angiography showed superior image quality (both readers, P < 0.05). Time-of-flight angiography enabled specific classification of PPA subtypes more often (53 vs 39; P < 0.05), and both readers reported higher diagnostic confidence for TOF angiography than CTA in all patients (interrater agreement κ = 0.8; P < 0.05). Regarding length assessment, PPAs were significantly more conspicuous with TOF angiography (TOFmean, 50 ± 11 mm; CTAmean, 40 ± 9 mm; P = 0.001). In comparison with CTA, TOF angiography prospectively changed the orofacial surgeon's final decision on the presurgical selected PPAs in 60% of cases.

Conclusions

Presurgical assessment of PPAs is feasible using TOF in 7 T magnetic resonance imaging. Moreover, TOF angiography was superior to CTA for classifying and identifying PPAs, which may facilitate the planning of reconstructive surgery.
A 3-Dimensional Measurements of Bone and Airway Variables After Le Fort I Distraction Osteogenesis in Patients With Cleft Lip and/or Palate-Induced Midface Hypoplasia: A Retrospective Study
Authors: Zhai Junya , Wang Binqing , Xu Meng , Zheng Yilue , Tong Haizhou , Yin Ningbei , Song Tao
Published: September 2022

The authors retrospectively analyzed the effects of Le Fort I advancement with distraction osteogenesis on skeletal and airway variables in patients with midfacial hypoplasia induced by cleft lip and/or palate using 3-dimensional computed tomography reconstructions.

The authors enrolled 23 subjects with moderate-to-severe midface hypoplasia induced by cleft lip and palate who were treated with Le Fort I distraction osteogenesis (mean age, 19.22±3.48 y; male/female ratio, 20/3); computed tomography images (1 before distraction and another at completion of distraction) were acquired. A 3-dimensional craniometric findings and airway volumes for the nasal cavity, nasopharynx, velopharynx, and upper and lower oropharynx were compared before and after distraction. The relationships between craniofacial morphology and changes in airway volume were also assessed (P<0.05 was considered significant).

Significant increases were observed in airway volumes for the nasal cavity (13.85%), nasopharynx (50.82%), velopharynx (29.57%), and upper oropharynx (36.92%) (P=0.007, P<0.001, P=0.023, and P<0.001, respectively), whereas no significant changes were observed for the lower oropharynx (P=0.117). Maxillary horizontal advancement was positively correlated with the airway volumes of the nasopharynx and upper oropharynx after distraction osteogenesis (rs=+0.451, P=0.031; rs=+0.548, P=0.007); however, no significant correlations were observed for the nasal cavity and velopharynx.

The authors’ finding indicate that despite rotation of the mandible along with the maxilla, this change does not impact airway volume at the mandibular level. Le Fort I distraction osteogenesis can be feasible for patients with cleft lip and palate-induced midface hypoplasia, with satisfactory appearance and occlusion. Long-term detailed follow-up of the patients postdistraction osteogenesis is warranted.
An Innovative Method for Nasal Alar Reduction Surgery Based on the Equilateral Triangle Design Theory
Authors: Guo Yu , Wang Heng , Chen Liang , Zhou Yiqun , Zhu Jingjing , Liu Tianyi
Published: September 2022

At present, there is no unified and accurate method to design the amount of tissue to be removed in alar reduction surgery. The authors present the experience that the crescent-shaped alar resection is based on the innovative equilateral triangle theory. It can accurately estimates the amount of alar tissue to be removed and conforms to the 3-dimensional esthetic concept of the nose. Followed up for 6 to 12 months, took 6 and 12 months postoperative photos, measured the postoperative nasal base width, and conduct a questionnaire satisfaction survey. The width of the nasal base was reduced by an average of 4.4±2.1 mm. The mean visual analog scale score showed: 4.8±1.6 before operation and 7.6±1.2 after the operation (P<0.05), which revealed satisfactory patient outcomes. This method provides a new idea for the evaluation of nasal alar resection volume and is worthy of clinical application.
ELEVATED PD-1/CD28 RATIO RATHER THAN PD-1 EXPRESSION IN CD8+ T CELLS PREDICTS NOSOCOMIAL INFECTION IN SEPSIS PATIENTS: A PROSPECTIVE, OBSERVATIONAL COHORT STUDY
Authors: Zhong Wenhong , Li Jing , Li Dongxin , Li Xusheng , Liu Mengting , Zhang Tiancao , Huang Junhong , Huang Guoge , Zeng Hongke , Zhou Maohua , Jiang Wenqiang
Published: September 2022

ABSTRACT—Background

The expression of programmed cell death 1 receptor (PD-1) and CD28 on CD8+ T cells is considered to be related to immune function and prognosis markers in patients with sepsis. However, the relationship between the ratio of PD-1/CD28 and nosocomial infection has not been elucidated. Methods: A prospective, observational cohort study was conducted in a general intensive care unit. Patients were enrolled according to the sepsis-3 criteria and peripheral blood samples were collected within 24 hours of enrollment. Programmed cell death 1 receptor and CD28 expression on CD8+ T cells was assayed on day 1. Patients were followed up until 28 days. Multivariate regression analysis was used to assess independent risk factors for nosocomial infection. The accuracy of biomarkers for nosocomial infection and mortality was determined by the area under the receiver operating characteristic curve analysis. The association between biomarkers and 28-day mortality was assessed by Cox regression survival analysis. Results: A total of 181 patients were recruited, and 68 patients were finally included for analysis. Of these, 19 patients (27.9%) died during 28 days and 22 patients (32.4%) acquired nosocomial infection. The PD-1/CD28 ratio of patients with nosocomial infection was significantly higher than those without (0.27 [0.10–0.55] vs. 0.15 [0.08–0.28], P = 0.025). The PD-1/CD28 ratio in CD8+ T cells (odds ratio, 53.33; 95% confidence interval, 2.39–1188.22, P = 0.012) and duration of mechanical ventilation (odds ratio, 1.14; 95% confidence interval, 1.06–1.24; P = 0.001) were independently associated with nosocomial infection. The area under the receiver operating characteristic curve of PD-1/CD28 ratio in CD8+ T cells was 0.67 (0.52–0.82). The PD-1/CD28 ratio in CD8+ T cells of the nonsurvivors was significantly higher than the survivors (0.23 [0.15–0.52] vs. 0.14 [0.07–0.32]); Cox regression analysis showed that the survival time of patients with PD-1/CD28 ratio in CD8+ T cells of 0.13 or greater was shorter compared with patients with lower levels (hazard ratio, 4.42 [1.29–15.20], χ2 = 6.675; P = 0.010). Conclusions: PD-1/CD28 ratio in CD8+ T cells at admission may serve as a novel prognostic biomarker for predicting nosocomial infection and mortality.
MILD TRAUMATIC BRAIN INJURY ATTENUATES PNEUMONIA-INDUCED LUNG INJURY BY MODULATIONS OF ALVEOLAR MACROPHAGE BACTERICIDAL ACTIVITY AND M1 POLARIZATION
Authors: Ruan Feng , Chen Jing , Yang Jianxin , Wang Guirong
Published: September 2022

Traumatic brain injury is one of the main causes of death and disability worldwide, and results in multisystem complications. However, the mechanism of mild traumatic brain injury (MTBI) on lung injury remains unclear. In this study, we used a murine model of MTBI and pneumonia (Pseudomonas aeruginosa;) to explore the relationship between these conditions and the underlying mechanism. Methods: Mice (n = 104) were divided into control, MTBI, pneumonia, and MTBI + pneumonia groups. MTBI was induced by the weight-drop method. Pneumonia was induced by intratracheal injection with P. aeruginosa Xen5 strain. Animals were killed 24 h after bacterial challenging. Histological, cellular, and molecular indices of brain and lung injury were assessed using various methods. Results: Mice in both the MTBI and pneumonia groups had more Fluoro-Jade C–positive neurons than did the controls (P < 0.01), but mice in the MTBI + pneumonia group had fewer Fluoro-Jade C–positive cells than did the pneumonia group (P < 0.01). The MTBI + pneumonia mice showed decreased bacterial load (P < 0.05), reduced lung injury score and pulmonary permeability (P < 0.01), less inflammatory cells, and lower levels of proinflammatory cytokines (TNF-α and IL-1β; P < 0.01) when compared with the pneumonia group. Molecular analysis indicated lower levels of phosphorylated nuclear factor-κB in the lung of MTBI + pneumonia mice compared with the pneumonia group (P < 0.01). Furthermore, alveolar macrophages from MTBI mice exhibited enhanced bactericidal capacity compared with those from controls (P < 0.01). Moreover, MTBI + pneumonia mice exhibited less CD86-positive M1 macrophages compared with the pneumonia group (P < 0.01). Conclusions: MTBI attenuates pneumonia-induced acute lung injury through the modulation of alveolar macrophage bactericidal capacity and M1 polarization in bacterial pneumonia model.
Fundidesulfovibrio magnetotacticus sp. nov., a sulphate-reducing magnetotactic bacterium, isolated from sediments and freshwater of a pond
Authors: Shimoshige Hirokazu , Kobayashi Hideki , Shimamura Shigeru , Miyazaki Masayuki , Maekawa Toru
Published: September 2022

A sulphate-reducing magnetotactic bacterium, designated strain FSS-1T, was isolated from sediments and freshwater of Suwa Pond located in Hidaka, Saitama, Japan. Strain FSS-1T was a motile, Gram-negative and curved rod-shaped bacterium that synthesizes bullet-shaped magnetite (Fe3O4) nanoparticles in each cell. Strain FSS-1T was able to grow in the range of pH 6.5–8.0 (optimum, pH 7.0), 22–34 °C (optimum, 28 °C) and with 0–8.0 g l−1 NaCl (optimum, 0–2.0 g l−1 NaCl). Strain FSS-1T grew well in the presence of 50 µM ferric quinate as an iron source. The major fatty acids were anteiso-C15 : 0, iso-C15 : 0 and anteiso-C17 : 0. The major menaquinone was MK-7 (H2). Strain FSS-1T contained desulfoviridin, cytochrome c
3 and catalase, but did not contain oxidase. Strain FSS-1T used fumarate, lactate, pyruvate, malate, formate/acetate, succinate, tartrate, ethanol, 1-propanol, peptone, soytone and yeast extract as electron donors, while the strain used sulphate, thiosulphate and fumarate as electron acceptors. Fumarate was fermented in the absence of electron acceptors. Analysis of the 16S rRNA gene sequence showed that strain FSS-1T is a member of the genus

Fundidesulfovibrio

. The gene sequence showed 96.7, 95.0, 92.0, 91.2 and 91.4% similarities to the most closely related members of the genera

Fundidesulfovibrio putealis

B7-43T,

Fundidesulfovibrio butyratiphilus

BSYT,

Desulfolutivibrio sulfoxidireducens

DSM 107105T,

Desulfolutivibrio sulfodismutans

ThAc01T and

Solidesulfovibrio magneticus

RS-1T, respectively. The DNA G+C content of strain FSS-1T was 67.5 mol%. The average nucleotide identity value between strain FSS-1T and

F. putealis

B7-43T was 80.7 %. Therefore, strain FSS-1T represents a novel species within the genus

Fundidesulfovibrio

, for which the name Fundidesulfovibrio magnetotacticus sp. nov. is proposed (=JCM 32405T=DSM 110007T).
Predicting the long-term impact of rotavirus vaccination in 112 countries from 2006-2034: a transmission modeling analysis
Authors: Kraay A.N.M. , Steele M.K. , Baker J.M. , Hall E.W. , Deshpande A. , Saidzosa B.F. , Mukaratirwa A. , Boula A. , Mpabalwani E. M. , Kiulia N.M. , Tsolenyanu E , Enweronu-Laryea C. , Abebe A. , Beyene B. , Tefera M. , Willilo R. , Batmunkh N. , Pastore R. , Mwenda J.M. , Antoni S. , Cohen A.L. , Pitzer V.E. , Lopman B.A.
Published: September 2022

Rotavirus vaccination has been shown to reduce rotavirus burden in many countries, but the long-term magnitude of vaccine impacts is unclear, particularly in low-income countries. We use a transmission model to estimate the long-term impact of rotavirus vaccination on deaths and disability adjusted life years (DALYs) from 2006-2034 for 112 low- and middle-income countries. We also explore the predicted effectiveness of a one- vs two-dose series and the relative contribution of direct vs indirect effects to overall impacts. To validate the model, we compare predicted percent reductions in severe rotavirus cases with the percent reduction in rotavirus positivity among gastroenteritis hospital admissions for 10 countries with pre- and post-vaccine introduction data. We estimate that vaccination would reduce deaths from rotavirus by 49.1% (95% UI: 46.6–54.3%) by 2034 under realistic coverage scenarios, compared to a scenario without vaccination. Most of this benefit is due to direct benefit to vaccinated individuals (explaining 69-97% of the overall impact), but indirect protection also appears to enhance impacts. We find that a one-dose schedule would only be about 57% as effective as a two-dose schedule 12 years after vaccine introduction. Our model closely reproduced observed reductions in rotavirus positivity in the first few years after vaccine introduction in select countries. Rotavirus vaccination is likely to have a substantial impact on rotavirus gastroenteritis and its mortality burden. To sustain this benefit, the complete series of doses is needed.
Predictive model for BNT162b2 vaccine response in cancer patients based on cytokines and growth factors
Authors: Konnova Angelina , De Winter Fien HR , Gupta Akshita , Verbruggen Lise , Hotterbeekx An , Berkell Matilda , Teuwen Laure-Anne , Vanhoutte Greetje , Peeters Bart , Raats Silke , Van der Massen Isolde , De Keersmaecker Sven , Debie Yana , Huizing Manon , Pannus Pieter , Neven Kristof Y , Ariën Kevin K , Martens Geert A. , Van Den Bulcke Marc , Roelant Ella , Desombere Isabelle , Anguille Sébastien , Berneman Zwi , Goossens Maria E , Goossens Herman , Malhotra-Kumar Surbhi , Taconelli Evelina , Vandamme Timon , Peeters Marc , van Dam Peter , Kumar-Singh Samir
Published: September 2022

Abstract

Background

Patients with cancer, especially haematological cancer, are at increased risk for breakthrough COVID-19 infection. However, so far, a predictive biomarker that can assess compromised vaccine-induced anti-SARS-CoV-2 immunity in cancer patients has not been proposed.

Methods

Here, we employed machine learning approaches to identify a biomarker signature based on blood cytokine and growth factors linked to vaccine response from 199 cancer patients receiving BNT162b2 vaccine.

Results

We show that C-reactive protein (CRP; general marker of inflammation), interleukin (IL)-15 (a pro-inflammatory cytokine), IL-18 (interferon-gamma inducing factor), and placental growth factor (an angiogenic cytokine) can correctly classify patients with a diminished vaccine response assessed at day 49 with >80% accuracy. Amongst these, CRP showed the highest predictive value for poor response to vaccine administration. Importantly, this unique signature of vaccine response was present at different studied timepoints both before and after vaccination and was not majorly affected by different anti-cancer treatments.

Conclusion

While we propose a blood-based signature of cytokines and growth factors that can be employed in identifying cancer patients at continued risk of COVID-19, our data also importantly suggest that such a signature could reflect the inherent make-up of some cancer patients who are also refractive to immunotherapy.
The additive effect of genetic modifiers on ALS prognosis: a population-based study
Authors: Chiò Adriano , Moglia Cristina , Canosa Antonio , Manera Umberto , Grassano Maurizio , Vasta Rosario , Palumbo Francesca , Gallone Salvatore , Brunetti Maura , Barberis Marco , De Marchi Fabiola , Dalgard Clifton , Chia Ruth , Mora Gabriele , Iazzolino Barbara , Peotta Laura , Traynor Bryan , Corrado Lucia , D’Alfonso Sandra , Mazzini Letizia , Calvo Andrea
Published: September 2022

Objective

To determine if the co-presence of genetic polymorphisms related to ALS has additive effects on the course of the disease in a population-based cohort of Italian patients.

Methods

The study population includes 1245 ALS patients identified through the Piemonte Register for ALS, diagnosed between 2007 and 2016 and not carrying SOD1, TARDBP and FUS mutations. Controls were 766 age, sex, and geographically matched Italian subjects. We considered UNC13A (rs12608932), CAMTA1 (rs2412208), SLC112A (rs407135) and ZNF512B (ZNF512B) polymorphisms, as well as ATXN2 polyQ intermediate repeats and C9ORF72 GGGGCC intronic expansion.

Results

The variants in C9orf72 (p=0.016), ATXN2 (p<0.001) and UNC13A (p<0.001) were significantly related to survival in univariate analysis, while the other considered variants did not influence ALS outcome. However, in the Cox multivariable analysis, also CAMTA1 emerged to be independently related to survival. When assessing the interaction by pairs of genes, we found that the presence of both detrimental alleles/expansion was correlated with significantly shorter survival compared to subjects non-carrying both detrimental alleles/expansions. Each association of pairs of detrimental alleles was characterized by specific clinical phenotypes.

Conclusions

we demonstrated that gene polymorphisms acting as genetic modifiers of ALS survival can act on their own or in unison. Overall, 54% of patients carried at least one detrimental common polymorphism or repeat expansion, highlighting the clinical impact of our findings. In addition, the identification of the synergic effects of modifier genes represents an essential clue for explaining ALS clinical heterogeneity and should be considered in designing and interpreting clinical trials.

Key messages

What is already known on this topic

Besides the disease-causing genes, several other genes have been reported to act as modifiers of ALS phenotype, especially patients’ survival. However, the interactions of these genes at clinical level have never been explored.

What this study adds

We demonstrated that gene polymorphisms and expansions acting as genetic modifiers of ALS survival can act on their own or in unison. Overall, 54% of patients carried at least one detrimental allele at common polymorphism or repeat expansion, highlighting the clinical impact of our findings.

How this study might affect research, practice, or polic

The identification of the synergic effects of modifier genes represents an essential clue for explaining ALS clinical heterogeneity, will have deep effects on clinical trial design and interpretation and support the inclusion of these polymorphisms in ALS genetic panels.
Impact of cellular prion protein expression on disease progression and pathology in two mouse models of Alzheimer’s disease
Authors: Purro Silvia A. , Farmer Michael , Noble Elizabeth , Sarell Claire J. , Powell Megan , Yip Daniel Chun-Mun , Giggins Lauren , Zakka Leila , Thomas David X. , Farrow Mark A. , Nicoll Andrew J. , Walsh Dominic , Collinge John
Published: September 2022

The aggregation of amyloid-β (Aβ) monomers increases their neurotoxicity, and these oligomeric species are thought to be central to the pathogenesis of Alzheimer’s disease. Unsurprisingly for such a complex disease, current Alzheimer’s disease mouse models fail to fully mimic the clinical disease in humans. Moreover, results obtained in a given mouse model are not always reproducible in a different model. Cellular prion protein (PrPC) is now an established receptor for Aβ oligomers. However, different groups studying the Aβ-PrPC interaction in vivo using a variety of mouse models have obtained contradictory results. Here we performed a longitudinal study in two commonly used AD mouse models using a range of biochemical, histological and behavioural techniques and found similar contradictory results and a possible explanation for the discrepancy. We propose that these two mouse models produce Aβ oligomers with different conformations. Therefore, binding to PrPC and the subsequent activation of toxic signalling cascade will occur only when the Aβ oligomer species with appropriate conformation are present. Hence, it is crucial to select the appropriate model producing the appropriate species of Aβ oligomers to study specific aspects of β-amyloidosis and its downstream pathways. Further conformational characterisation of Aβ oligomers and their binding to PrPC is required to better understand Aβ neurotoxicity.
Comprehensive structural analysis reveals broad-spectrum neutralizing antibodies against Omicron
Authors: Chi Xiangyang , Xia Lingyun , Zhang Guanying , Chi Ximin , Huang Bangdong , Zhang Yuanyuan , Chen Zhengshan , Han Jin , Wu Liushu , Li Zeya , Sun Hancong , Huang Ping , Yu Changming , Chen Wei , Zhou Qiang
Published: September 2022

The pandemic of COVID-19 caused by SARS-CoV-2 continues to spread around the world. Mutant strains of SARS-CoV-2 are constantly emerging. At present, Omicron variants have become mainstream. In this work, we carried out a systematic and comprehensive analysis of the reported spike protein antibodies, counting the antibodies’ epitopes and genotypes. We further comprehensively analyzed the impact of Omicron mutations on antibody epitopes and classified these antibodies according to their binding patterns. We found that the epitopes of one class of antibodies were significantly less affected by Omicron mutations than other classes. Binding and virus neutralization experiments show that such antibodies can effectively inhibit the immune escape of Omicron. Cryo-EM results show that this class of antibodies utilizes a conserved mechanism to neutralize SARS-CoV-2. Our results greatly help us deeply understand the impact of Omicron mutations. At the same time, it also provides guidance and insights for developing Omicron antibodies and vaccines.
“Primed to Perform:” Dynamic white matter graph communicability may drive metastable network representations of enhanced preparatory cognitive control
Authors: Buch Vivek P. , Bernabei John M. , Ng Grace , Richardson Andrew G. , Ramayya Ashwin , Brandon Cameron , Stiso Jennifer , Bassett Danielle S. , Lucas Timothy H.
Published: September 2022

Spontaneous neural activity has become increasingly linked to behavioral and cognitive output. A specific cognitive control mode, proactive control, uses prior information to plan and prepare the brain to be particularly sensitive to incoming goal-directed stimuli. Little is known about specific proactive mechanisms implemented via preparatory patterns of spontaneous neural activity, that may enable dynamically enhanced cognitive performance. In this study, humans implanted with intracranial electrodes performed a simple cognitive task. For each subject, pre-trial spectral power and communicability-based features from both grey and white matter nodes were extracted to identify preparatory control states that were “primed to perform”. The anatomical structure and topology of these states across subjects demonstrated a critical role for white matter communicability in decoding and intrinsically controlling preparatory network activity. Our results provide novel insights for putative cognitive network control and may be studied to develop prosthetic approaches for individuals with cognitive deficits.
Quantifying Spatio-Temporal Overlap of Invasive Wild Pigs and Domestic Pig Farms as a Proxy for Potential Disease Transmission Risk
Authors: Aschim Ruth A. , Brook Ryan K.
Published: September 2022

Direct and indirect interactions between livestock and free-ranging wildlife creates important risks to animal health and agricultural productivity. The interface between newly established and rapidly spreading invasive wild pigs and the 2,549 domestic pig farms on the Prairie Provinces of western Canada has created important but poorly understood disease transmission risks. We mapped the spatial overlap of wild and domestic pigs to identify the areas of highest risk and associated distribution of diseases of concern using databases of wild pig occurrences and domestic pig farm locations. We also examined spatial and temporal overlap at the individual farm scale using GPS collared invasive wild pigs. Across the provinces of Alberta, Saskatchewan, and Manitoba, spatial overlap of invasive wild pigs with all combined, large-scale domestic pig farms, small-scale domestic pig farms, and domestic wild boar farms was 21%, 21%, 21%, and 53%. Invasive wild pig locations were significantly closer to domestic pig farms and domestic wild boar farms compared to random points on the landscape. The number of wild pig occurrences was greatest within 20 km of domestic pig farms and decreased linearly as distance increased. The Canadian distribution of wild pigs had considerable spatial overlap with recent areas detected with bovine tuberculosis (6,002 km2) in livestock and wildlife and Chronic Wasting Disease (156,159 km2) in wildlife, including mule deer, white-tailed deer, elk, and moose. The single best predictor of invasive wild pig occurrences across the landscape was close proximity to current or recently past existing domestic wild boar farms. The distance of GPS- collared wild pigs was significant for sex, farm type, month, and season and in southeastern Saskatchewan, average distance to domestic pig farms was 5.3 km. The weighted sum of cover type proportions, wild pig distance to domestic pig and wild boar farms, farm type, and farm density identified the relative risk of wild pig presence associated to each domestic pig farm occupied watershed. Risk was highest for small-scale domestic pig farms and lowest for large- scale domestic pig farms. Our findings highlight important potential routes for disease transmission at the invasive wild pig-domestic pig interface and identify areas where biosecurity improvements are urgently needed. While complete eradication of invasive wild pigs in Canada is no longer achievable, improved passive and active monitoring and removal of wild pigs is critical, especially where risks to domestic pig herds is highest.
Heterogeneity of burst firing in mouse thalamic reticular nucleus neurons
Authors: Harding-Jackson Laura M. , Beatty Joseph A. , Cox Charles L.
Published: September 2022

The thalamic reticular nucleus (TRN) sits at the interface of the thalamus and neocortex and provides the majority of inhibition to thalamic relay nuclei. Functionally, the activity of TRN neurons can impact sensory processing and may influence arousal states. TRN neurons discharge action potentials in two distinct output modes: tonic or burst firing. Burst output, a transient high frequency discharge of action potentials, is dependent on the activation of transient low-threshold voltage-dependent T-type calcium current (IT). In our current study, we identify a broad range of burst firing frequencies in TRN neurons, which depend on the activation of IT. The amplitude of the low-threshold calcium spike (LTS) underlying the burst positively correlated with burst frequency and number of action potentials per burst. Activation of small conductance calcium-activated potassium (SK) channels on TRN neurons can impact burst discharge. Attenuation of SK channels increased TRN neuron burst frequency through an increase in LTS duration, but not magnitude. The broad range of burst firing frequencies could provide distinct downstream inhibition within thalamic nuclei.
An Improved Algorithm for Inferring Mutational Parameters from Bar-Seq Evolution Experiments
Authors: Li Fangfei , Mahadevan Aditya , Sherlock Gavin
Published: September 2022

Genetic barcoding provides a high-throughput way to simultaneously track the frequencies of large numbers of competing and evolving microbial lineages. However making inferences about the character of the evolution that is taking place remains a difficult task. Here we describe a step toward more accurate inference of fitness effects and establishment times of beneficial mutations, which builds upon a prior method by enforcing self-consistency between the population mean fitness and the individual effects of mutations within lineages. By testing our inference method on a simulation of 40,000 barcoded lineages evolving in serial batch culture, we find that this new method outperforms its predecessor, identifying more adaptive mutations and more accurately inferring their mutational parameters. We have made available our code for the joint Bayesian inference of population mean fitness and lineage-specific mutational parameters, in the hope that it can find broader use by the microbial evolution community.
A non-ligand surrogate agonist antibody that enhances canonical Wnt signaling and bone regeneration
Authors: Lee Nam-Kyung , Bidlingmaier Scott , Su Yang , Seo Youngho , Liu Bin
Published: September 2022

The Wnt signaling pathway promotes tissue regeneration and is a promising therapeutic target for treatment of osteolytic bone diseases. Here we report the discovery of a novel type of canonical Wnt agonist antibody that does not operate as a ligand surrogate. The antibody increases Wnt/β-catenin signaling with or without exogenously provided Wnt ligands. It binds to a site on the P3 domain of LRP6 that is distinct from where the Wnt3a ligand and the DKK1 antagonist bind. The agonist effect persists in the presence of DKK1 and is further amplified by R-spondin even when Wnt ligands are not provided, suggesting a potential use for this antibody in ligand-low or insufficient settings. The antibody induces osteoblastic differentiation and mineralization in vitro and restores bone loss in vivo in a myeloma-derived intrafemoral mouse model, opening a potential path for therapeutic development in osteolytic diseases caused by cancer and aging.
Household transmission of SARS-CoV-2 during the Omicron wave in Shanghai, China:a case-ascertained study
Authors: Wei Zhongqiu , Ma Wenjie , Wang Zhonglin , Li Jingjing , Fu Xiaoming , Chang Hailing , Qiu Yue , Tian He , Ge Yanling , Zhu Yanfeng , Xia Aimei , Wu Qianhui , Liu Gongbao , Zhai Xiaowen , Zhang Xiaobo , Wang Yan , Zeng Mei
Published: September 2022

Background

Since late 2021, the highly transmissible SARS-CoV-2 Omicron variant has driven a new surge of infections across the world. We used a case-ascertained study to determine the features of household transmission of SARS-CoV-2 Omicron variant in Shanghai, China.

Methods

We collected detailed information on 323 pediatric cases and their 951 household members in April 2022 during the Omicron outbreak. All household members received consecutively intensive RT-PCR testing for SARS-CoV-2 and routine symptom monitoring within 14 days after exposure to a confirmed case. We described the characteristics of study participants and estimated the transmission parameters. Both secondary infection attack rates (SARI) and secondary clinical attack rates (SARC) among adult household contacts were computed, through which the transmission heterogeneities in infectivity and susceptibility were characterized and the vaccine effectiveness were estimated.

Results

We estimated the mean incubation period of SARS-CoV-2 Omicron variant to be 4.6 (median: 4.4, IQR: 3.1-6.0) days and the mean serial interval to be 3.9 (median:4.0, IQR: 1.4-6.5) days. The overall SARI and SARC among adult household contacts were 77.11% (95% confidence interval [CI]: 73.58%-80.63%) and 67.03% (63.09%-70.98%). We found higher household susceptibility in females, while infectivity was not significantly different in primary cases by age, sex, vaccination status and clinical severity. The estimated VEs of full vaccination was 14.8% (95% CI: 5.8%-22.9%) against Omicron infection and 21.5% (95% CI: 10.4%-31.2%) against symptomatic disease. The booster vaccination was 18.9% (95% CI: 9.0%-27.7%) and 24.3% (95% CI: 12.3%-34.7%) effective against infection and symptomatic disease, respectively.

Conclusions

We found high household transmission during the Omicron wave in Shanghai due to asymptomatic and pre-symptomatic transmission in the context of city-wide lockdown, indicating the importance of early detection and timely isolation of SARS-CoV-2 infections and quarantine of close contacts. Marginal effectiveness of inactivated vaccines against Omicron infection poses great challenge for prevention and control of the SARS-CoV-2 Omicron variant.