bluuebunny/crossref_metadata_2025 huggingface dataset:
GRN300–001: Phase 1/1B evaluation of the safety, pharmacokinetics, and efficacy of GRN-300, a salt-inducible kinase inhibitor, alone and in combination with paclitaxel, in recurrent ovarian, primary peritoneal, and fallopian tube cancers.
Authors: Fu Siqing , Jazaeri Amir A. , Lu Zhen , Peter Markus , Morris Stephan Wade , Bast Robert C.
Published: June 2022

TPS5616

Background: Salt-induced kinase 2 (SIK2) is a serine-threonine kinase that regulates centrosome splitting, activation of PI3 kinase and phosphorylation of Class IIa HDACs. SIK2 is overexpressed in 30% of ovarian cancers and associated with decreased progression-free survival (Ahmed et al., 2010). Treatment with GRN-300, an orally bioavailable small-molecule inhibitor of SIK2, was shown to improve the response to paclitaxel in human ovarian cancer cells grown in culture and in immunocompromised mice (Zhou et al., 2017). Methods: Part 1 of the study will evaluate the safety, MTD, RP2D (Recommended Phase 2 Dose), and PK of daily GRN-300 monotherapy. For the dose-escalation enrollment of patients with advanced solid tumors of any histology, four dose levels of GRN-300 are planned: 100, 200, 300, and 400 mg BID. Subsequently, GRN-300 will be administered at the determined RP2D in an ovarian cancer expansion cohort. Part 2 will evaluate the safety, PK, and preliminary clinical activity in an open-label study of the combination of GRN-300 and paclitaxel weekly x3. Paclitaxel will be administered in one of two different dosing levels: 60 mg/m2 initially, then dose escalated to 80 mg/m2. In the combination regimen, GRN-300 will be administered at the RP2D dose as determined in Part 1 of this study. The two dose findings will be conducted independently using the BOIN design (Liu 2015, Yuan 2016). Study drug may be administered per protocol for continuous 28-day cycles until disease progression, adverse events, or other criteria as described in the protocol. Tumor biopsies and blood plasma samples including peripheral blood mononuclear cells (PBMCs) will be collected for exploratory biomarker analysis to predict and to monitor responses to GRN-300 treatment. Major eligibility criteria At least 18 years of age. Recurrent or persistent, locally non-resectable or metastatic ovarian, primary peritoneal or fallopian tube epithelial cancer (advanced solid tumors of any other histology only for the monotherapy dose escalation enrollment in Part 1) In Part 2, diagnosis of recurrent or persistent, locally non-resectable or metastatic ovarian, primary peritoneal or fallopian tube epithelial cancer for which treatment with paclitaxel is indicated. Received at least one prior second-line treatment. The first 3 dose groups (100, 200, and 300 mg BID of GRN-300) have been completed without DLT and preliminary PK analysis indicate dose proportionality. Enrollment to dose group 4 (400 mg BID) began in February 2022. Clinical trial information: NCT04711161.
A phase 1/2 study of VS-6766 (RAF/MEK clamp) in combination with sotorasib (G12C inhibitor) in patients with KRAS G12C mutant non–small cell lung cancer (NSCLC) (RAMP 203).
Authors: Govindan Ramaswamy , Awad Mark M. , Gadgeel Shirish M. , Pachter Jonathan A. , Patrick Gloria , Denis Louis J.
Published: June 2022

TPS9148

Background: KRAS is mutated (mt) in 25% of non-small cell lung cancer (NSCLC) adenocarcinoma, with KRAS G12C mt occurring in ̃13% of patients. The G12C inhibitor (G12Ci) sotorasib has recently received FDA approval for patients with KRAS G12C NSCLC. Several studies have shown that simultaneous targeting of multiple nodes in the RAS pathway may be optimal for durable pathway inhibition and response. Furthermore, acquired mutations and amplifications in the RAS pathway occur clinically upon progression on sotorasib or adagrasib. Accordingly, combination of G12Ci with a downstream blocker of the RAS pathway may be needed for more durable response. VS-6766 is a unique small molecule RAF/MEK clamp that inhibits BRAF, CRAF and MEK, enabling VS-6766 to block MEK signaling more consistently without the compensatory activation of MEK that reduces the efficacy of MEK-only inhibitors. In vitro 3D proliferation and in vivo tumor models were used to assess anti-tumor efficacy of VS-6766 ± G12Ci. In KRAS G12C mt NSCLC cell lines, VS-6766 was synergistic with both sotorasib and adagrasib in reducing tumor cell viability which correlated with deeper inhibition of RAS pathway signaling. In vivo, combination of VS-6766 with sotorasib induced strong tumor regressions in contrast to sotorasib monotherapy or sotorasib plus trametinib. Initial clinical activity of VS-6766 in KRAS G12C mt NSCLC is supported by the FRAME study [NCT03875820] results, in which 4/6 patients with KRAS G12C mt NSCLC showed tumor reduction including 1 PR. These results support the clinical evaluation of VS-6766 in combination with a G12Ci for treatment of KRAS G12C mt NSCLC. Methods: This is a Phase 1/2, multicenter, open label, dose evaluation/dose expansion study designed to evaluate the efficacy and safety of VS-6766 in combination with sotorasib in patients with KRAS G12C mt NSCLC who have not previously been treated with a KRAS G12Ci or have experienced disease progression while undergoing therapy with a KRAS G12Ci [NCT05074810]. The study will be conducted in two parts: Part A (dose evaluation) and Part B (dose expansion). Up to 3 dose levels will be evaluated in Part A to determine the Recommended Phase 2 Dose (RP2D) for Part B. Part B will assess the efficacy of the RP2D and will be conducted in 2 cohorts: patients who are G12Ci treatment naïve (cohort 1) and patients who have experienced disease progress during G12Ci therapy (Cohort 2). Patients enrolled must have histologic or cytologic evidence of NSCLC, measurable disease according to RECIST V1.1 and known KRAS G12C mutation. The study will enroll up to 121 patients with a minimum of 6 and a maximum of 12 patients in Part A and an additional 109 patients in Part B (minimum of 41 patients at RP2D stage 1 for cohort 1 and 2 or RP2D stages 1 and 2 in both cohorts). Clinical trial information: NCT05074810.
Adiposity, Insulin Resistance, Cardiorespiratory Fitness, and Bone Health in Hispanic Children
Authors: Shawar Reem S , Puyau Maurice , Shypailo Roman , Musaad Salma , Butte Nancy F , Bacha Fida
Published: June 2022

Context

Childhood obesity disproportionately affects Hispanic youth. The skeletal system appears to be a target organ of the adverse effects of obesity. Yet, the relationship between adiposity and bone health in youth and the modulating factors are not well understood.

Objective

This work aims to examine the relationship between adiposity, insulin resistance (IR), cardiorespiratory fitness (CRF), and bone mass in Hispanic youth.

Methods

A total of 951 Hispanic youth (50% male), aged 4 to 19 years, participated in this cross-sectional design study from the Viva La Familia Study at Children’s Nutrition Research Center. Bone mineral content (BMC) and density (BMD), lean mass (LM), total body fat mass (FM), truncal FM were obtained using dual-energy x-ray absorptiometry. Fasting glucose and insulin were obtained and the homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. CRF was measured using a treadmill ramp protocol. We applied linear regression models and mediation analyses.

Results

Adiposity measures were negatively related to BMC and BMD after accounting for LM and sex. IR negatively contributed whereas CRF positively contributed to the variance in BMC and BMD, more notably in the pubertal age group. In mediation analysis, HOMA-IR partially mediated the negative relationship of adiposity to BMC (standardized indirect effect [IE] = –0.0382; 95% CI, –0.0515 to –0.0264) whereas the sequential IE of HOMA-IR and CRF partially attenuated (IE = –0.0026; 95% CI, –0.0053 to –0.0005) this relationship. Similar findings were seen with BMD as the primary outcome.

Conclusion

IR mediates the negative relationship between adiposity and bone mass whereas CRF may partially attenuate it.
Vitamin D receptor absence does not enhance intestinal tumorigenesis in ApcPirc/+rats
Authors: Irving Amy A. , Waters Bayley J. , Seeman Jeremy R. , Plum Lori A. , DeLuca Hector F.
Published: June 2022

Epidemiological observations have prompted some to posit that elevated circulating vitamin D is responsible for reduced colon cancer in individuals residing near the equator. We have previously demonstrated that vitamin D has no effect on colon cancer in two rodent models of intestinal tumorigenesis. We have now extended this line of inquiry to ask whether ablation of vitamin D receptor (VDR) affects tumorigenesis. A VDR null rat was developed using Cas9-CRISPR technology, which allowed us to investigate whether 1,25(OH)D3 signaling through its receptor plays a role in intestinal tumorigenesis. Loss of VDR expression alone did not induce tumorigenesis, even in animals exposed to the inflammatory agent dextran sodium sulfate. These VDR−/− rats were then crossed with ApcPirc/+ rats, which are predisposed to the development of intestinal neoplasms. In combination with the Pirc/+ mutation, VDR loss did not enhance tumor multiplicity, growth, or progression in the colon or small intestine. This study demonstrates that the vitamin D receptor does not impact tumor development, and strongly supports previous findings that vitamin D itself does not play a role in colon cancer development or progression. Alternative explanations are needed for the original latitude hypothesis, as well as observational data in humans.

This article has an associated First Person interview with the first author of the paper.
A prominent gene activation role for C-terminal binding protein in mediating PcG/trxG proteins through Hox gene regulation
Authors: Bi Cai-Li , Cheng Qian , Yan Ling-Yue , Wu Hong-Yan , Wang Qiang , Wang Ping , Cheng Lin , Wang Rui , Yang Lin , Li Jian , Tie Feng , Xie Hao , Fang Ming
Published: June 2022

The evolutionarily conserved C-terminal binding protein (CtBP) has been well characterized as a transcriptional co-repressor. Herein, we report a previously unreported function for CtBP, showing that lowering CtBP dosage genetically suppresses Polycomb group (PcG) loss-of-function phenotypes while enhancing that of trithorax group (trxG) in Drosophila, suggesting that the role of CtBP in gene activation is more pronounced in fly development than previously thought. In fly cells, we show that CtBP is required for the derepression of the most direct PcG target genes, which are highly enriched by homeobox transcription factors, including Hox genes. Using ChIP and co-IP assays, we demonstrate that CtBP is directly required for the molecular switch between H3K27me3 and H3K27ac in the derepressed Hox loci. In addition, CtBP physically interacts with many proteins, such as UTX, CBP, Fs(1)h and RNA Pol II, that have activation roles, potentially assisting in their recruitment to promoters and Polycomb response elements that control Hox gene expression. Therefore, we reveal a prominent activation function for CtBP that confers a major role for the epigenetic program of fly segmentation and development.
Sperm-specific glycogen synthase kinase 3 is required for sperm motility and the post-fertilization signal for female meiosis II in Caenorhabditis elegans
Authors: Banerjee Rudra Prasanna , Srayko Martin
Published: June 2022

In most sexually reproducing animals, sperm entry provides the signal to initiate the final stages of female meiosis. In Caenorhabditis elegans, this signal is required for completion of female anaphase I and entry into meiosis II (MII). memi-1/2/3 (meiosis-to-mitosis) encode maternal components that facilitate this process; memi-1/2/3(RNAi) results in a skipped-MII phenotype. Previously, we used a gain-of-function mutation, memi-1(sb41), to identify genetic suppressors that represent candidates for the sperm-delivered signal. Herein, we characterize two suppressors of memi-1(sb41): gskl-1 and gskl-2. Both genes encode functionally redundant sperm glycogen synthase kinase, type 3 (GSK3) protein kinases. Loss of both genes causes defects in male spermatogenesis, sperm pseudopod treadmilling and paternal-effect embryonic lethality. The two kinases locate within the pseudopod of activated sperm, suggesting that they directly or indirectly regulate the sperm cytoskeletal polymer major sperm protein (MSP). The GSK3 genes genetically interact with another memi-1(sb41) suppressor, gsp-4, which encodes a sperm-specific PP1 phosphatase, previously proposed to regulate MSP dynamics. Moreover, gskl-2 gsp-4; gskl-1 triple mutants often skip female MII, similar to memi-1/2/3(RNAi). The GSK3 kinases and PP1 phosphatases perform similar sperm-related functions and work together for post-fertilization functions in the oocyte that involve MEMI.
A unifying model for the role of the ATG8 system in autophagy
Authors: Nguyen Thanh Ngoc , Lazarou Michael
Published: June 2022

The formation of autophagosomes and their fusion with lysosomes are key events that underpin autophagic degradation of cargoes. The core ATG8 system, which consists of the ATG8 family of ubiquitin-like proteins and the machineries that conjugate them onto autophagosomal membranes, are among the most-studied autophagy components. Despite the research focus on the core ATG8 system, there are conflicting reports regarding its essential roles in autophagy. Here, we reconcile prior observations of the core ATG8 system into a unifying model of their function that aims to consider apparently conflicting discoveries. Bypass pathways of autophagy that function independently of the core ATG8 system are also discussed.
Understanding how variable thermal environments affect the molecular mechanisms underlying temperature-sensitive phenotypes: lessons from sex determination
Authors: Paitz Ryan T. , Breitenbach Anthony T. , Marroquín-Flores Rosario A. , Bowden Rachel M.
Published: June 2022

The thermal environment that organisms experience can affect many aspects of their phenotype. As global temperatures become more unpredictable, it is imperative that we understand the molecular mechanisms by which organisms respond to variable, and often transient, thermal environments. Beyond deciphering the mechanisms through which organisms respond to temperature, we must also appreciate the underlying variation in temperature-dependent processes, as this variation is essential for understanding the potential to adapt to changing climates. In this Commentary, we use temperature-dependent sex determination as an example to explore the mechanistic processes underlying the development of temperature-sensitive phenotypes. We synthesize the current literature on how variable thermal conditions affect these processes and address factors that may limit or allow organisms to respond to variable environments. From these examples, we posit a framework for how the field might move forward in a more systematic way to address three key questions: (1) which genes directly respond to temperature-sensitive changes in protein function and which genes are downstream, indirect responders?; (2) how long does it take different proteins and genes to respond to temperature?; and (3) are the experimental temperature manipulations relevant to the climate the organism experiences or to predicted climate change scenarios? This approach combines mechanistic questions (questions 1 and 2) with ecologically relevant conditions (question 3), allowing us to explore how organisms respond to transient thermal environments and, thus, cope with climate change.
Is vertebral shape variability in caecilians (Amphibia: Gymnophiona) constrained by forces experienced during burrowing?
Authors: Lowie Aurélien , De Kegel Barbara , Wilkinson Mark , Measey John , O'Reilly James C. , Kley Nathan J. , Gaucher Philippe , Brecko Jonathan , Kleinteich Thomas , Adriaens Dominique , Herrel Anthony
Published: June 2022

Caecilians are predominantly burrowing, elongate, limbless amphibians that have been relatively poorly studied. Although it has been suggested that the sturdy and compact skulls of caecilians are an adaptation to their head-first burrowing habits, no clear relationship between skull shape and burrowing performance appears to exist. However, the external forces encountered during burrowing are transmitted by the skull to the vertebral column, and, as such, may impact vertebral shape. Additionally, the muscles that generate the burrowing forces attach onto the vertebral column and consequently may impact vertebral shape that way as well. Here, we explored the relationships between vertebral shape and maximal in vivo push forces in 13 species of caecilian amphibians. Our results show that the shape of the two most anterior vertebrae, as well as the shape of the vertebrae at 90% of the total body length, is not correlated with peak push forces. Conversely, the shape of the third vertebrae, and the vertebrae at 20% and 60% of the total body length, does show a relationship to push forces measured in vivo. Whether these relationships are indirect (external forces constraining shape variation) or direct (muscle forces constraining shape variation) remains unclear and will require quantitative studies of the axial musculature. Importantly, our data suggest that mid-body vertebrae may potentially be used as proxies to infer burrowing capacity in fossil representatives.
Importance of Overall Activity and Intensity of Activity for Cardiometabolic Risk in Those with and Without a Chronic Disease
Authors: DAWKINS NATHAN P. , YATES TOM , EDWARDSON CHARLOTTE L. , MAYLOR BEN , HENSON JOSEPH , HALL ANDREW P. , DAVIES MELANIE J. , DUNSTAN DAVID W. , HIGHTON PATRICK J. , HERRING LOUISA Y. , KHUNTI KAMLESH , ROWLANDS ALEX V.
Published: June 2022

Introduction

Higher levels of physical activity are associated with lower cardiometabolic risk. However, the relative contribution of overall activity and the intensity of activity are unclear. Our aim was to determine the relative contribution of overall activity and intensity distribution of activity to cardiometabolic risk in a cross-sectional analysis of apparently healthy office workers and in people with one or more chronic disease.

Methods

Clustered cardiometabolic risk score was calculated from mean arterial pressure, high-density lipoprotein cholesterol, triglycerides and HbA1c. Open-source software (GGIR) was used to generate average acceleration and intensity gradient from wrist-worn accelerometer data for two data sets: office-workers who did not have a self-reported medical condition (n = 399, 70% women) and adults with one or more chronic disease (n = 1137, 34% women). Multiple linear regression analyses were used to assess the relative contribution of overall activity and intensity of activity to cardiometabolic risk.

Results

When mutually adjusted, both overall activity and intensity of activity were independently associated with cardiometabolic risk in the healthy group (P < 0.05). However, for the CD group, although mutually adjusted associations for average acceleration were significantly associated with cardiometabolic risk (P < 0.001), intensity was not. In healthy individuals, cardiometabolic risk was lower in those with high overall activity and/or intensity of activity, and who also undertook at least 10 min brisk walking. In those with a chronic disease, risk was lower in those who undertook at least 60 min slow walking.

Conclusions

These findings suggest interventions aiming to optimize cardiometabolic health in healthy adults could focus on increasing both intensity and amount of physical activity. However, in those with chronic disease, increasing the amount of activity undertaken, regardless of intensity, may be more appropriate.
The genetic causes of male infertility: a Middle East and North Africa perspective
Authors: Duvuru Ruthwik , Halabi Mouhammad , Omolaoye Temidayo S. , Du Plessis Stefan S.
Published: June 2022

Male infertility is attributable to 60% of total infertility cases and about 30-50% of these cases remain idiopathic. In the Middle East and North Africa region (MENA), male infertility affects about 22.6% of men of reproductive age. Male infertility is caused by a variety of factors, including endocrine disruption, exposure to toxins, lifestyle, genetic and epigenetic modifications. Genetic modifications, including chromosomal abnormalities, chromosomal rearrangements, Y chromosome microdeletions and single-gene mutations, explain for about 10-15% of infertility cases. Since genetic aberration is a key player in the pathogenesis of male infertility, it is important to explore the impact in the MENA region due to the high incidence of male infertility. Therefore, the current study aims to systematically analyse the literature regarding the impact and common causes of male infertility in the MENA region. To achieve this aim, a comprehensive literature search was performed on PubMed, Google Scholar, and Science Direct databases. Following the search, a total of 126 articles was retrieved, of which 12 were duplicates and another 69 articles did not meet the inclusion criteria, totaling the exclusion of 81 articles. Studies excluded were those that had patient populations originating outside the MENA region, review articles, non-English written articles, or studies where the patient population was under 18 years of age.

Findings showed that the frequent genetic aberration leading to male infertility in these regions include Y chromosome microdeletions, gene polymorphisms or copy number variations, mitochondrial microdeletions and other genetic deletions or mutations. In lieu of this, diverse clinical genetic tests should be made available for the proper diagnosis of male infertility.
Unprecedented early-summer heat stress and forecast of coral bleaching on the Great Barrier Reef, 2021-2022
Authors: Spady Blake L. , Skirving William J. , Liu Gang , De La Cour Jacqueline L. , McDonald Cathy J. , Manzello Derek P.
Published: June 2022

The Great Barrier Reef (GBR) is predicted to undergo its sixth mass coral bleaching event during the Southern Hemisphere summer of 2021-2022. Coral bleaching-level heat stress over the GBR is forecast to start earlier than any previous year in the satellite record (1985-present). The National Oceanic and Atmospheric Administration (NOAA) Coral Reef Watch (CRW) near real-time satellite-based heat stress products were used to investigate early-summer sea surface temperature (SST) and heat stress conditions on the GBR during late 2021. As of 14 December 2021, values of instantaneous heat stress (Coral Bleaching HotSpots) and accumulated heat stress over a 12-week running window (Degree Heating Weeks) on the GBR were unprecedented in the satellite record. Further, 89% of GBR satellite reef pixels for this date in 2021 had a positive seven-day SST trend of greater than 0.2 degrees Celsius/week. Background temperatures (the minimum temperature over the previous 29 days) were alarmingly high, with 87% of GBR reef pixels on 14 December 2021 being greater than the maximum SST over that same 29-day period for any year from 1985-2020. The GBR is starting the 2021-2022 summer season with more accumulated heat than ever before, which could have disastrous consequences for the health, recovery, and future of this critical reef system.
The complete genome sequence of elite bread wheat cultivar, “Sonmez”
Authors: Akpinar Bala Ani , Leroy Philippe , Watson-Haigh Nathan , Baumann Ute , Barbe Valerie , Budak Hikmet
Published: June 2022

High-yielding crop varieties will become critical in meeting the future food demand in the face of worsening weather extremes and threatening biotic stressors. The bread wheat cultivar Sonmez-2001 is a registered variety that is notable for its performance under low-irrigation conditions, which further improves upon irrigation. Additionally, Sonmez-2001 is resilient against certain biotic stressors, particularly soil-borne pathogens.

Here, we provide a reference-guided whole genome sequence of Sonmez-2001, assembled into 21 chromosomes of the A, B and D genomes and totaling 13.3 gigabase-pairs in length. Additionally, a de novo assembly of an additional 1.05 gigabase-pairs was generated that represents either Sonmez-specific sequences or sequences that considerably diverged between Sonmez and Chinese Spring. Within this de novo assembly, we identified 35 gene models, of which 11 were high-confidence, that may contribute to the favorable traits of this high-performing variety. We identified up to 24 million sequence variants, of which up to 2.4% reside in coding sequences, that can be used to develop molecular markers that should be of immediate use to the cereal community.
Case Report: Takotsubo cardiomyopathy in a postoperative patient without cardiological disease
Authors: Coaguila-Cusicanqui Luis , Castillo-Atoche Vanessa , Montalvo-Suyon Roberto , Cavero-Reyes Yuriko , Failoc-Rojas Virgilio E.
Published: June 2022

Background: Takotsubo cardiomyopathy (TC) is characterized by a clinical presentation that mimics acute coronary syndrome but is reversible. Alterations of Takotsubo in patients without previous heart disease remain a challenge for diagnosis.

Case report: We present a case of an 80-year-old patient from Peru. The patient underwent surgery, with the diagnosis of Chilaiditi’s syndrome. One day after surgery, she presented with dyspnea, tachycardia, and electrocardiographic changes. The diagnosis of Takotsubo syndrome with cardiogenic shock and renal failure on hemodialysis was made. She was hospitalized in the Intensive Care Unit and was managed with vasopressors and nitroglycerin. There was no cardiac lesion in the cineangiogram or occlusion of arteries. The patient was extubated and received daily dialysis until discharge.

Conclusions: Takotsubo is an emotional, non-cardiac, or post-traumatic stressful event that triggers myocardial injury with segmental anomalous, the possible etiology of which is the release of an endothelial neurotransmitter caused by stress. Emergency physicians should be aware of this as even patients without previous cardiac pathologies when exposed to stressors (such as surgeries) develop emergency symptomatology similar to myocardial infarction. Thus, emergency physicians should identify any cardiac abnormalities after a stressor, as well as be prepared for the diagnosis of TC.
Farmers’ knowledge, perceptions, and practices on animal trypanosomosis and the tsetse fly vector: A cross-sectional study around Kenya’s Arabuko-Sokoke Forest Reserve at the livestock-wildlife interface
Authors: Serem Erick K , Bargul Joel L , Ngari Moses M , Abdullahi Osman A , Mburu David M
Published: June 2022

Background: Animal African trypanosomosis (AAT) is a veterinary disease caused by trypanosomes transmitted cyclically by tsetse flies. AAT causes huge agricultural losses in sub-Saharan Africa. Both tsetse flies and trypanosomosis (T&T) are endemic in the study area inhabited by smallholder livestock farmers at the livestock-wildlife interface around Arabuko-Sokoke Forest Reserve (ASFR) in Kilifi County on the Kenyan coast. We assessed farmers’ knowledge, perceptions and control practices towards T&T.

Methods: A cross-sectional study was conducted during November and December 2017 to collect data from 404 randomly selected cattle-rearing households using a structured questionnaire. Descriptive statistics were used to determine farmers’ knowledge, perceptions, and control practices towards T&T. Demographic factors associated with knowledge of T&T were assessed using a logistic regression model.

Results: Participants consisted of 53% female, 77% married, 30% elderly (>55 years), and the majority (81%) had attained primary education or below. Most small-scale farmers (98%) knew the tsetse fly by its local name, and 76% could describe the morphology of the adult tsetse fly by size in comparison to the housefly’s (Musca domestica). Only 16% of the farmers knew tsetse flies as vectors of livestock diseases. Higher chances of adequate knowledge on T&T were associated with the participants’ (i) age of 15–24 years (aOR 2.88 (95% CI 1.10–7.52), (ii) level of education including secondary (aOR 2.46 (95% CI 1.43–4.24)) and tertiary (aOR 3.80 (95% CI 1.54–9.37)), and (iii) employment status: self-employed farmers (aOR 6.54 (95% CI 4.36–9.80)).

Conclusions: Our findings suggest that small-scale farmers around ASFR have limited knowledge of T&T. It is envisaged that efforts geared towards training of the farmers would bridge this knowledge gap and sharpen the perceptions and disease control tactics to contribute to the prevention and control of T&T.
Prognosis of postoperative course of urolithiasis
Authors: BEREZhNOY Aleksandr , DUNAEVSKAYa Svetlana , VINNIK Yuriy
Published: June 2022

The monograph devoted to the study of urolithiasis consistently highlights the issues of etiology, classification, diagnosis and modern principles of treatment of urolithiasis. The problems of postoperative complications in surgery and urology are considered as a separate issue, data on original methods for predicting the development of hemorrhagic or inflammatory complications in the postoperative period with urolithiasis are presented. Special attention is paid to the issues of nonspecific immune protection, immune status indicators and hemostasis system in the development of complications in the postoperative period. The section of assessment of the structural and functional state of lymphocytes in the development of complications in the postoperative period by assessing the blebbing of the plasma membrane of the cell is presented.
It is intended for urologists, general surgeons, residents studying in the specialty "Urology". It can be useful for doctors of other specialties and senior students of higher medical educational institutions.
CAD programming: Spatial modeling of the air cooling device in the Autodesk Inventor environment
Authors: Lyang Viktor
Published: June 2022

The tutorial discusses in detail the creation of an external subsystem for Autodesk Inventor in a high-level C# Microsoft Visual Studio language of a low-flow air cooling device. Such issues as working in the Microsoft Visual Studio 2010 programming environment, connecting the library of Autodesk Inventor API functions to an external user subsystem, spatial solid-state modeling of elements of the air cooling apparatus, saving constructed objects, assembling the apparatus from stored modules using the interface of basic coordinate planes are considered.
Meets the requirements of the federal state educational standards of higher education of the latest generation.
For students studying in the field of Computer Science and Computer Engineering, in preparation for laboratory work and exam. It can be used by students of other specialties when studying the courses "Fundamentals of Computer Science", "High-level programming language" and "3D modeling of machines and apparatuses". It is useful for programmers who are engaged in spatial modeling of objects.
Modyfikacje konstrukcji stabilizującej reguły wydatkowej w 2021 roku
Authors: Ostrowski Michał
Published: June 2022

Przedmiotem artykułu jest analiza zmian w art. 112aa i art. 112d ustawy o finansach publicznych, które zostały uchwalone na mocy ustawy z dnia 11 sierpnia 2021 r. o zmianie ustawy o finansach publicznych oraz niektórych innych ustaw. Na wstępie krótkiemu opisowi została poddana konstrukcja mechanizmu SRW oraz nakreślone zostały jego wcześniejsze zmiany. Następnie dogłębnej analizie poddane zostały przyczyny i forma każdej z omawianych zmian. Na tej podstawie zostały wyciągnięte wnioski co do wpływu modyfikacji na funkcjonowanie stabilizującej reguły wydatkowej w następnych latach.
Cost-utility analysis of cast compared to removable brace in the management of adult patients with ankle fractures
Authors: Nwankwo Henry , Mason James , Costa Matthew L. , Parsons Nicholas , Redmond Anthony , Parsons Helen , Haque Aminul , Kearney Rebecca S.
Published: June 2022

Aims

To compare the cost-utility of removable brace compared with cast in the management of adult patients with ankle fracture.

Methods

A within-trial economic evaluation conducted from the UK NHS and personnel social services (PSS) perspective. Health resources and quality-of-life data were collected as part of the Ankle Injury Rehabilitation (AIR) multicentre, randomized controlled trial over a 12-month period using trial case report forms and patient-completed questionnaires. Cost-utility analysis was estimated in terms of the incremental cost per quality adjusted life year (QALY) gained. Estimate uncertainty was explored by bootstrapping, visualized on the incremental cost-effectiveness ratio plane. Net monetary benefit and probability of cost-effectiveness were evaluated at a range of willingness-to-pay thresholds and visualized graphically.

Results

The incremental cost and QALYs of using brace over a 12-month period were £46.73 (95% confidence interval (CI) £-9 to £147) and 0.0141 (95% CI -0.005 to 0.033), respectively. The cost per QALY gained was £3,318. The probability of brace being cost-effective at a £30,000 per QALY willingness-to-pay threshold was 88%. The results remained robust to a range of sensitivity analyses.

Conclusion

This within-trial economic evaluation found that it is probable that using a removable brace provides good value to the NHS when compared to cast, in the management of adults with ankle fracture. Cite this article: Bone Jt Open 2022;3(6):455–462.
Non-blind optical degradation correction via frequency self-adaptive and finetune tactics
Authors: Lin Ting , Chen ShiQi , Feng Huajun , Xu Zhihai , Li Qi , Chen Yueting
Published: June 2022

In mobile photography applications, limited volume constraints the diversity of optical design. In addition to the narrow space, the deviations introduced in mass production cause random bias to the real camera. In consequence, these factors introduce spatially varying aberration and stochastic degradation into the physical formation of an image. Many existing methods obtain excellent performance on one specific device but are not able to quickly adapt to mass production. To address this issue, we propose a frequency self-adaptive model to restore realistic features of the latent image. The restoration is mainly performed in the Fourier domain and two attention mechanisms are introduced to match the feature between Fourier and spatial domain. Our method applies a lightweight network, without requiring modification when the fields of view (FoV) changes. Considering the manufacturing deviations of a specific camera, we first pre-train a simulation-based model, then finetune it with additional manufacturing error, which greatly decreases the time and computational overhead consumption in implementation. Extensive results verify the promising applications of our technique for being integrated with the existing post-processing systems.
Long-range high-speed laser imaging based on VCSEL array and MPPC array
Authors: Tang Yumei , Fu Zeyu , Yang Runze , Zhao Hui , Qiu JIAN , Liu Kefu
Published: June 2022

Flash LiDAR is a photoelectric system that can acquire a 3D image by emitting a diffuse pulsed laser beam, and hence is suitable for both autopilot and spacecraft flight control. Achieving long-range and high-speed, especially in outdoor applications with strong solar background illumination, are challenging requirements. In this paper, a set of laser imaging prototype based on 2×6 VCSEL array and 32×32 MPPC array image sensor is developed, the range calibration is completed, and relevant experimental research is carried out. The frame rate of the system can reach 10kHz, the detection probability of 120m range can reach 86.23%, and the maximum walk error is about 0.6m under different reflectivity. The 3D imaging of the vehicle can be realized at about 70m, the horizontal spatial resolution is less than 5cm, and the ranging precision after ten shots average is within 10cm by calculating the centroid of a histogram. The detection probability can be improved by using the time-gating method. After multiple measurements, a 120m “laser imaging through window” can be realized in sunlight. This LiDAR system has the advantages of small volume, light weight and fast detection speed.
Mitigating the ambiguity problem in the CNN-based wavefront correction
Authors: Lu Chenda , Tian Qinghua , Zhu Lei , Gao Ran , Yao Haipeng , Tian Feng , Zhang Qi , Xin Xiangjun
Published: June 2022

In this work, we propose an attention-based adaptive optics method that uses a non-local block to integrate phase diversity with a convolutional neural network (CNN). The simulation results showcase the effectiveness of the proposed method to mitigate the ambiguity problem of phase retrieval and better performance than traditional CNN-based wavefront correction.
Chemical bath synthesis of Ag2S, CuS, and CdS nanoparticle-polymer nanocomposites: structural, linear, and nonlinear optical characteristics
Authors: Fatemi Ali , Rasouli Milad , Ghoranneviss Mahmood , Dorranian Davoud , Ostrikov Kostya (Ken)
Published: June 2022

In this study, CdS, CuS, and Ag2S nanoparticles (NPs) were
synthesized by a chemical bath procedure in the presence of polyvinyl
alcohol (PVA) as a polymer stabilizer. Morphological studies followed
by X-ray diffraction (XRD) and atomic force microscopy (AFM) revealed
monolithic and small size NPs. The average crystalline size of CdS,
Ag2S, and CuS nanocomposites was 18.1, 26.7, and 21.7 nm,
respectively. UV-Vis absorption and photoluminescence (PL) spectra of
samples showed a near-infrared region (NIR) emission peak for CuS. The
bandgap of samples measured using absorption data was 3.48, 2.75, and
2.30 eV for CdS, Ag2S, and CuS NPs, respectively. Nonlinear
optical properties, including nonlinear refractive index and nonlinear
absorption of the NPs, were measured by the Z-scan technique under a
632.8 nm wavelength He-Ne CW laser. PVA/Ag2S nanocomposite
displayed reverse saturable absorbance (RSA) and self-focusing, while
PVA/CdS and PVA/CuS displayed saturable absorbance and self-defocusing
behavior under the chemical bath procedure synthesis.
The phospho-docking protein 14-3-3 regulates microtubule-associated proteins in oocytes including the chromosomal passenger Borealin
Authors: Repton Charlotte , Cullen C. Fiona , Costa Mariana F. A. , Spanos Christos , Rappsilber Juri , Ohkura Hiroyuki
Published: June 2022

Global regulation of spindle-associated proteins is crucial in oocytes due to the absence of centrosomes and their very large cytoplasmic volume, but little is known about how this is achieved beyond involvement of the Ran-importin pathway. We previously uncovered a novel regulatory mechanism inDrosophilaoocytes, in which the phospho-docking protein 14-3-3 suppresses microtubule binding of Kinesin-14/Ncd away from chromosomes. Here we report systematic identification of microtubule-associated proteins regulated by 14-3-3 fromDrosophilaoocytes. Proteins from ovary extract were co-sedimented with microtubules in the presence or absence of a 14-3-3 inhibitor. Through quantitative mass-spectrometry, we identified proteins or complexes whose ability to bind microtubules is suppressed by 14-3-3, including the chromosomal passenger complex (CPC), the centralspindlin complex and Kinesin-14/Ncd. We showed that 14-3-3 binds to the disordered region of Borealin, and this binding is regulated differentially by two phosphorylations on Borealin. Mutations at these two phospho-sites compromised normal Borealin localisation and centromere bi-orientation in oocytes, showing that phospho-regulation of 14-3-3 binding is important for Borealin localisation and function.
A role for the mitotic proteins Bub3 and BuGZ in transcriptional regulation of catalase-3 expression
Authors: Zhou Yike , Shen Shuangjie , Du Chengcheng , Wang Ying , Liu Yi , He Qun
Published: June 2022

The spindle assembly checkpoint factors Bub3 and BuGZ play critical roles in mitotic process, but little is known about their roles in other cellular processes in eukaryotes. In aerobic organisms, transcriptional regulation of catalase genes in response to developmental or environmental stimuli is necessary for redox homeostasis. Here, we demonstrate that Bub3 and BuGZ negatively regulate cat-3 transcription in the model filamentous fungus Neurospora crassa. The absence of Bub3 caused a significant decrease in BuGZ protein levels. Our data indicate that BuGZ and Bub3 interact directly via the GLEBS domain of BuGZ. Despite loss of the interaction, the amount of BuGZ mutant protein negatively correlated with the cat-3 expression level, indicating that BuGZ amount rather than Bub3-BuGZ interaction determines cat-3 transcription level. Further experiments demonstrated that BuGZ binds directly to the cat-3 gene and responses to cat-3 overexpression induced by oxidative stresses. However, the zinc finger domains of BuGZ have no effects on DNA binding, although mutations of these highly conserved domains lead to loss of cat-3 repression. The deposition of BuGZ along cat-3 chromatin hindered the recruitment of transcription activators GCN4/CPC1 and NC2 complex, thereby preventing the assembly of the transcriptional machinery. Taken together, our results establish a mechanism for how mitotic proteins Bub3 and BuGZ functions in transcriptional regulation in a eukaryotic organism.
One Health and surveillance of zoonotic tuberculosis in selected low-income, middle-income and high-income countries: A systematic review
Authors: de Macedo Couto Rodrigo , Santana Giulia Osório , Ranzani Otavio T. , Waldman Eliseu Alves
Published: June 2022

Background

Little is known about zoonotic tuberculosis (zTB) due to Mycobacterium bovis burden across the globe. The aim of this study was to describe zTB surveillance programs in selected WHO signatory countries and to assess the relationship of the disease with the country’s income level and the risk of M. bovis transmission.

Methods

We searched the main articles databases and grey literature for guide documents published between 1980 and 2019. For inclusion, the articles and guide documents had to be in English, French, Portuguese, Spanish, or Italian. Only original articles and narrative and systematic reviews were accepted and the guide documents were required to be available on official websites. We excluded articles that did not focus on epidemiology, control and surveillance. We used bovine TB cases in livestock and wildlife populations as a proxy for the country’s risk of zTB using data from the World Organization for Animal Health (OIE) published from 2015 to 2018. Countries were classified according to income level (World Bank’s classification) and strength of zTB surveillance. The study was registered in PROSPERO under number CRD42018090603.

Findings

We included 13 articles and 208 guide documents including data from 119/194 countries (61.3%). We found a lack of surveillance data about zTB in over half (89.9%) of the 119 WHO signatory countries. Most surveillance systems perform passive surveillance and are not integrated into the One Health perspective, which was operating in 4/119 (3.4%) countries, all high-income. Many of these countries (71/119, 59.7%) have M. bovis circulating in their cattle herds, but only ~10% of them have implemented zTB surveillance activities.

Interpretation

Our findings highlight weaknesses in zTB surveillance worldwide, with a consequent lack of information that could support an adequate understanding of disease burden, especially in countries at major risk for M. bovis transmission. To meet this challenge, efforts will be needed to promote intersectoral policies, implementing the One Health strategy.
Insecticide Resistance Profiles and Synergism of Field Aedes aegypti from Indonesia
Authors: Silalahi Christina Natalina , Tu Wu-Chun , Chang Niann-Tai , Singham G. Veera , Ahmad Intan , Neoh Kok-Boon
Published: June 2022

Information on the insecticide resistance profiles of Aedes aegypti in Indonesia is fragmentary because of the lack of wide-area insecticide resistance surveillance. We collected Ae. aegypti from 32 districts and regencies in 27 Indonesian provinces and used WHO bioassays to evaluate their resistance to deltamethrin, permethrin, bendiocarb, and pirimiphos-methyl. To determine the possible resistance mechanisms of Ae. aegypti, synergism tests were conducted using piperonyl butoxide (PBO) and S,S,S-tributylphosphorotrithioates (DEF). The Ae. aegypti from all locations exhibited various levels of resistance to pyrethroids. Their resistance ratio (RR50) to permethrin and deltamethrin ranged from 4.08× to 127× and from 4.37× to 72.20×, respectively. In contrast with the findings of other studies, most strains from the highly urbanized cities on the island of Java (i.e., Banten, Jakarta, Bandung, Semarang, Yogyakarta, and Surabaya) exhibited low to moderate resistance to pyrethroids. By contrast, the strains collected from the less populated Kalimantan region exhibited very high resistance to pyrethroids. The possible reasons are discussed herein. Low levels of resistance to bendiocarb (RR50, 1.24–6.46×) and pirimiphos-methyl (RR50, 1.01–2.70×) were observed in all tested strains, regardless of locality. PBO and DEF synergists significantly increased the susceptibility of Ae. aegypti to permethrin and deltamethrin and reduced their resistance ratio to less than 16×. The synergism tests suggested the major involvement of cytochrome P450 monooxygenases and esterases in conferring pyrethroid resistance. On the basis of our results, we proposed a 6-month rotation of insecticides (deltamethrin + synergists ➝ bendiocarb ➝ permethrin + synergists ➝ pirimiphos-methyl) and the use of an insecticide mixture containing pyrethroid and pyrimiphos-methyl to control Ae. aegypti populations and overcome the challenge of widespread Ae. aegypti resistance to pyrethroid in Indonesia.
A comparison of risk factors for cryptosporidiosis and non-cryptosporidiosis diarrhoea: A case-case-control study in Ethiopian children
Authors: Johansen Øystein Haarklau , Abdissa Alemseged , Zangenberg Mike , Mekonnen Zeleke , Eshetu Beza , Sharew Bizuwarek , Moyo Sabrina , Sommerfelt Halvor , Langeland Nina , Robertson Lucy J. , Hanevik Kurt
Published: June 2022

Background

Cryptosporidiosis is a major cause of diarrhoea in young children in low-and-middle-income countries. New interventions should be informed by evidence pertaining to risk factors and their relative importance. Inconsistencies in the literature may to some extent be explained by choice of methodology, furthermore, most previous risk factor studies compared cryptosporidiosis cases to diarrhoea cases of other aetiologies rather than with controls without diarrhoea.

Methodology/Principal findings

We investigated a broad set of factors in under-2-year-olds presenting with diarrhoea to a hospital and a health center in southwestern Ethiopia. We applied quantitative cut-offs to distinguish between cryptosporidiosis and incidental Cryptosporidium infection or carriage, a hierarchical causal framework to minimize confounding and overadjustment, and a case-case-control design, to describe risk factors for both cryptosporidiosis and non-cryptosporidiosis diarrhoea. Moderate and severe acute malnutrition were strongly associated with both cryptosporidiosis and non-cryptosporidiosis diarrhoea. Previous healthcare attendance and low maternal education were only associated with cryptosporidiosis, whereas unsafe child stool disposal, prematurity and early cessation of exclusive breastfeeding were significantly associated with non-cryptosporidiosis diarrhoea only. By estimation of population attributable fractions, socioeconomic factors—specifically low maternal education—and public tap water use, were apparently more important risk factors for cryptosporidiosis than for non-cryptosporidiosis diarrhoea.

Conclusions/Significance

Nutritional management of moderate acute malnutrition may be an effective intervention against cryptosporidiosis, particularly if combined with targeted therapy for cryptosporidiosis which, again, may mitigate nutritional insult. Focused caregiver education in healthcare settings and follow-up of children with acute malnutrition may prevent or improve outcomes of future episodes of cryptosporidiosis.