bluuebunny/crossref_metadata_2025 huggingface dataset:
Haptoglobin is an early indicator of survival after radiation-induced severe injury and bone marrow transplantation in mice
Authors: Zhou Shixiang , Li Yaqiong , He Lexin , Chen Min , Li Weihong , Xiao Ting , Guan Jian , Qi Zhenhua , Wang Qi , Li Siyuan , Zhou Pingkun , Wang Zhidong
Published: September 2022

Background

Hematopoietic stem cell transplantation (HSCT) is the main treatment for acute radiation sickness, especially after fatal radiation. The determination of HSCT for radiation patients is mainly based on radiation dose, hemogram and bone marrow injury severity. This study aims to explore a better biomarker of acute radiation injury from the perspective of systemic immune response.

Methods

C57BL/6J female mice were exposed to total body irradiation (TBI) and partial body irradiation (PBI). Changes in haptoglobin (Hp) level in plasma were shown at different doses and time points after the exposure and treatment with amifostine or bone marrow transplantation. Student’s t-test/two tailed test were used in two groups. To decide the Hp levels as a predictor of the radiation dose in TBI and PBI, multiple linear regression analysis were performed. The ability of biomarkers to identify two groups of different samples was determined by the receiver operating characteristic (ROC) curve. The results were expressed as mean ± standard deviation (SD). Significance was set at P value < 0.05, and P value < 0.01 was set as highly significant. Survival distribution was determined by log-rank test.

Results

In this study, we found that Hp was elevated dose-dependently in plasma in the early post-irradiation period and decreased on the second day, which can be used as a molecular indicator for early dose assessment. Moreover, we detected the second increase of Hp on the 3rd and 5th days after the lethal irradiation at 10 Gy, which was eliminated by amifostine, a radiation protection drug, while protected mice from death. Most importantly, bone marrow transplantation (BMT) on the 3rd and 5th day after 10 Gy radiation improved the 30-days survival rate, and effectively accelerated the regression of secondary increased Hp level.

Conclusions

Our study suggests that Hp can be used not only as an early molecule marker of radiation injury, but also as an important indicator of bone marrow transplantation therapy for radiation injury, bringing new scientific discoveries in the diagnosis and treatment of acute radiation injury from the perspective of systemic immunity.
Optimization of COVID-19 prevention and control measures during the Beijing 2022 Winter Olympics: a model-based study
Authors: Kong Lingcai , Duan Mengwei , Shi Jin , Hong Jie , Zhou Xuan , Yang Xinyi , Zhao Zheng , Huang Jiaqi , Chen Xi , Yin Yun , Li Ke , Liu Yuanhua , Liu Jinggang , Wang Xiaozhe , Zhang Po , Xie Xiyang , Li Fei , Chang Zhaorui , Zhang Zhijie
Published: September 2022

Background

The continuous mutation of severe acute respiratory syndrome coronavirus 2 has made the coronavirus disease 2019 (COVID-19) pandemic complicated to predict and posed a severe challenge to the Beijing 2022 Winter Olympics and Winter Paralympics held in February and March 2022.

Methods

During the preparations for the Beijing 2022 Winter Olympics, we established a dynamic model with pulse detection and isolation effect to evaluate the effect of epidemic prevention and control measures such as entry policies, contact reduction, nucleic acid testing, tracking, isolation, and health monitoring in a closed-loop management environment, by simulating the transmission dynamics in assumed scenarios. We also compared the importance of each parameter in the combination of intervention measures through sensitivity analysis.

Results

At the assumed baseline levels, the peak of the epidemic reached on the 57th day. During the simulation period (100 days), 13,382 people infected COVID-19. The mean and peak values of hospitalized cases were 2650 and 6746, respectively. The simulation and sensitivity analysis showed that: (1) the most important measures to stop COVID-19 transmission during the event were daily nucleic acid testing, reducing contact among people, and daily health monitoring, with cumulative infections at 0.04%, 0.14%, and 14.92% of baseline levels, respectively (2) strictly implementing the entry policy and reducing the number of cases entering the closed-loop system could delay the peak of the epidemic by 9 days and provide time for medical resources to be mobilized; (3) the risk of environmental transmission was low.

Conclusions

Comprehensive measures under certain scenarios such as reducing contact, nucleic acid testing, health monitoring, and timely tracking and isolation could effectively prevent virus transmission. Our research results provided an important reference for formulating prevention and control measures during the Winter Olympics, and no epidemic spread in the closed-loop during the games indirectly proved the rationality of our research results.

Graphical Abstract
Discrepancy between distribution of alpha-synuclein oligomers and Lewy-related pathology in Parkinson’s disease
Authors: Sekiya Hiroaki , Tsuji Asato , Hashimoto Yuki , Takata Mariko , Koga Shunsuke , Nishida Katsuya , Futamura Naonobu , Kawamoto Michi , Kohara Nobuo , Dickson Dennis W. , Kowa Hisatomo , Toda Tatsushi
Published: September 2022

The pathological hallmarks of Parkinson’s disease (PD) are α-synuclein (αSYN)-positive inclusions referred to as Lewy bodies and Lewy neurites, collectively referred to as Lewy-related pathology (LRP). LRP is thought to propagate in an ascending manner throughout the brain as the disease progresses. LRP is visible with histologic methods and is thought to represent a later stage of the disease process, while αSYN oligomers, which are not visible with routine histologic methods, are considered earlier. There is increasing evidence to suggest that αSYN oligomers may be more toxic than visible LRP. Detecting αSYN oligomers requires special techniques, and their distribution and association with clinical features are important research objectives. In this report, we describe the distribution of αSYN oligomers in multiple cortical and subcortical regions of PD using a proximity ligation assay (PLA). We observe widespread distribution of αSYN oligomers with PLA and more restricted distribution of LRP with αSYN immunohistochemistry. The distribution of αSYN oligomers differed from LRP in that αSYN oligomer burden was significantly greater in the neocortex, while LRP was greater in vulnerable subcortical regions, including the brainstem. We also found that cognitive impairment was associated with αSYN oligomers in the hippocampus. These results suggest that αSYN oligomers may be widely distributed in PD early in the disease process and that they may contribute to cognitive impairment in PD.
Consideration of health literacy in patient information: a mixed-methods study of COVID-19 crisis communication in Dutch rheumatology
Authors: Bakker Mark Matthijs , Luttikhuis Tess , Putrik Polina , Jansen Isabelle , Rademakers Jany , de Wit Maarten , Boonen Annelies
Published: September 2022

Background

The rapid spread of COVID-19 required swift action to provide people with rheumatic and musculoskeletal diseases (RMDs) with reliable information. People with limited health literacy constitute a vulnerable group that might have difficulty accessing, understanding and applying health information, particularly in times of crisis.

Objectives

This study explored (a) key aspects of crisis communication and (b) explicit consideration of people’s health literacy needs in communication to people with RMDs during the first wave of COVID-19 in the Netherlands.

Methods

We conducted a convergent, qualitatively driven mixed-methods study comprising seven qualitative interviews with professional representatives of organisations responsible for information provision to people with RMDs, and quantitative analysis of 15 patient information materials distributed by these organisations. The study was guided by principles of crisis communication and health literacy. We assessed understandability and actionability of information materials using the Dutch version of the Patient Education Materials Assessment Tool (PEMAT, resulting in a percentage of quality criteria met), and language difficulty level using an online application (assessing difficult words, jargon, passive, complex and long sentences, long paragraphs, and difficulty levels according to the Common European Framework of Reference for Languages (CEFR, from A1 (basic) to C2 (proficient))).

Results

Respondents reported lack of preparedness, challenges related to scientific uncertainty and reaching the target group, difficulty simplifying information, and uncertainty regarding adequacy of the communication approach. Patient information materials (written and video) showed variation in actionability (range 60–100%) and understandability (range 58–100%), and 69% of written materials were too difficult, mostly due to the use of long sentences and difficult words. The quantitative findings were in coherence with the limitations in communication reported by respondents. Several potential improvements were formulated in ‘lessons learned’.

Conclusions

Although rheumatology organisations mostly adhered to principles of crisis communication and made efforts to adapt information to their audience’s needs, we propose recommendations to improve preparedness, strategy, content, reach and consideration of health literacy needs in future crisis communication.
Prevalence and associated factors of depression among people with epilepsy in Ethiopia: a cross-sectional study
Authors: Seid Jemal , Mebrahtu Kalayu
Published: September 2022

Background

Depression is the most common comorbid psychiatric disorders that affect people with epilepsy. We aim to determine the prevalence of depression and associated factors among people with epilepsy.

Results

The prevalence of depression was found to be 34.8%. Unable to read and write (AOR = 0.400, 95% CI: 0.162, 0.986), long duration of the medication intake at least for 11 years (AOR = 3.715, 95% CI: 1.498, 9.212), absence of improvement with antiepileptic drugs (AOR = 0.216, 95% CI: 0.101, 0.460), feeling of perceived stigma (AOR = 0.244, 95% CI: 0.129, 0.462), stress symptoms (AOR = 0.452, 95% CI: 0.220, 0.928), were significantly associated with depression.

Conclusions

Prevalence of depression among people with epilepsy was high. Therefore, early screening and management is mandatory. This is the first research study, to our knowledge, that evaluates the association between substance use, sexual and physical abuse among people with epilepsy with depression. Therefore, future research needs to investigate the association.
Percutaneous coronary artery intervention in unprotected left main coronary artery disease: one-year outcome Egyptian registry
Authors: Ayman Rana , Shaheen Sameh Mohamed , Sabet Sameh Saleh , Abdellatif Yasser A.
Published: September 2022

Background

Left main coronary artery lesions are associated with jeopardy of an outsized area of the myocardium, causing a high incidence of morbidity and mortality. Optimal treatment of coronary bifurcation anatomy remains highly debatable, whether by provisional or two-stent technique. This prospective observational study was designed to investigate the one-year clinical outcomes of unprotected left main coronary artery disease revascularization by percutaneous coronary intervention in a “real-world” setting among Egyptian patients in a prospective single-center registry (at Ain Shams University Hospitals).

Results

This study included 163 patients who underwent PCI to LM lesions between May 1, 2020, and the end of April in Ain Shams University hospitals. Patients were dichotomized into two groups according to their intended stenting technique, whether provisional or two-stent technique. A total of 142 underwent provisional stenting while 21 were designated for the two-stent technique, mainly DK crush (double kissing). Among the patients with intended provisional stenting, 34 patients underwent the TAP technique. Patients were followed up for the primary endpoints, at the in-hospital setting, at 30 days, and after 1 year. In-hospital death was encountered in 6.34% of cases undergoing provisional stenting, among which 5.36% were due to a cardiovascular cause. Total MACCE was found to be 2.96% in the provisional stenting group versus 4.76% in the two-stent group. Overall, MACCE at 1 year was found to be 22.31% in the provisional group and 30% in the two-stent group (p-value0.57). TVF was recognized in 10% of cases treated by provisional stenting and 30% of cases treated by the two-stent technique (p-value 0.023).

Conclusions

LM coronary artery lesions treatment by PCI is considered a safe and beneficial solution. Provisional stenting is the preferred approach bearing in mind that bail-out procedures may be sought in case the SB needs further treatment. Adjunctive assessment by IVUS or FFR may help achieve better outcomes, and efforts should be performed to facilitate their feasibility.
Drugs acting on the renin–angiotensin–aldosterone system (RAAS) and deaths of COVID-19 patients: a systematic review and meta-analysis of observational studies
Authors: Sharma Ruchika , Kumar Anoop , Majeed Jaseela , Thakur Ajit K. , Aggarwal Geeta
Published: September 2022

Background

Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) are two of the most commonly used antihypertensive drugs acting on the renin–angiotensin–aldosterone system (RAAS). Previous research has shown that RAAS inhibitors increase the expression of angiotensin-converting enzyme, a cellular receptor for the severe acute respiratory syndrome coronavirus 2, raising concerns that the use of ACEi and ARBs in hypertensive patients may increase COVID-19 patient mortality. Therefore, the main aim of the current study was to find out the role of drugs acting on RAAS, particularly ACEi/ARBs in the deaths of COVID-19 patients.

Results

In total, 68 studies were found to be appropriate, reporting a total of 128,078 subjects. The odds ratio was found to be 1.14 [0.95, 1.36], which indicates the non-significant association of ACEi/ARBs with mortality of COVID-19 patients. Further, the association of individual ACEi/ARBs with mortality of COVID-19 patients was also found non-significant. The sensitivity analysis results have shown no significant effect of outliers on the outcome.

Conclusions

Based on available evidence, ACEi/ARB were not significantly associated with deaths of COVID-19 patients.
Congenital nodular fasciitis: an extremely rare entity with review of literature
Authors: Wagner Till , Ulrich Dietmar
Published: September 2022

Background

Nodular fasciits is thought to be a benign superficial nodular disease, which most often occurs in the medium age of adolescence, mainly in the subcutaneous or fascial plane on the upper extremities and trunk. The percentage of this entity in children compared to adults is less than 10%. Most cases in childhood were reported at the head and neck region, therefore often renamed to cranial or extracranial fasciitis. These lesions often consists of sarcoma like structures. Preoperative imaging is often unspecific and the standard of treatment in children is biopsy or in some cases complete resection with narrow margin depending on size or location of the lesion.

Case presentation

We present a clinical case of a female newborn with a congenital nodular presternal mass. Biopsy revealed nodular fasciits by testing on USP6 gen rearrangement. With ongoing growth of her nodular thoracic tumor, she underwent complete resection with primary closure. We followed her clinical course over more than 3 years and give a review of the literature.

Conclusion

Only a minority of reports are documented with a neonate onset and none with a real congenital. We hereby presented the first case in literature of a proven congenital fasciits other than cranial/extracranial in a newborn and her clinical course.
End-of-Life Health Resource Utilization for Limited English-Proficient Patients With Advanced Non–Small-Cell Lung Cancer
Authors: Leung Bonnie , Wong Selina K. , Ho Cheryl
Published: September 2022

PURPOSE:

Limited English-proficient (LEP) patients with non–small-cell lung cancer (NSCLC) may receive less palliative care services and more likely to receive aggressive end-of-life (EoL) care. Goals of this retrospective cohort study are to compare access to community palliative home care (CPHC), do not resuscitate (DNR) form completion, place of death, and health resource utilization at EoL between English-proficient (EP) and LEP patients with NSCLC in Vancouver, Canada.

METHODS:

All patients with advanced NSCLC referred in 2016 and received medical care were included. Patients were classified as LEP if seen with a medical interpreter. Descriptive statistics and univariate and multivariate analyses were used to compare the outcomes between the two groups.

RESULTS:

One hundred eighty-six patients were referred, 66% EP. Rates of CPHC referral and DNR form completion were the same for both groups (84% and 92%, P = 1.00). LEP patients received earlier access to CPHC (15 v 10 weeks before death, P = .039). Rates of ER visits within 6 months and 30 days of death were 0.89 for EP patients and 0.7 for LEP patients, P = .374, and 0.1 for EP patients and 0.13 for LEP patients, P = .244. Hospitalization rates within 6 months and 30 days of death were 1.4 for EP patients and 1.59 for LEP patients, P = .640, and 0.67 for EP patients and 0.81 for LEP patients, P = .091. EP patients were more likely to have a home death (26% v 14%), whereas LEP patients died in acute care (23% v 14%) or a tertiary palliative care unit (24% v 19%). This was not statistically significant ( P = .335). LEP patients had better median overall survival (8.5 v 5.4 months, P < .001), but when controlled by age, mutation, and EP status, only receipt of palliative-intent systemic therapy was statistically significant.

CONCLUSION:

EP and LEP patients with NSCLC have similar referral rates to CPHC, DNR form completion, and EoL health resource utilization. The measured EoL variables did not demonstrate significant disparities between EP and LEP patients.
Low Serum Bicarbonate Levels Increase the Risk of All-Cause, Cardiovascular Disease, and Cancer Mortality in Type 2 Diabetes
Authors: Li Yilan , Gao Rong , Zhao Bing , Zhang Yao
Published: September 2022

Context

The evidence regarding bicarbonate status and mortality among diabetes is scarce.

Objective

The purpose of this study was to investigate the associations of bicarbonate concentrations with risk of all-cause, cardiovascular disease (CVD), and cancer mortality among patients with type 2 diabetes (T2D).

Methods

This study included 8163 adult diabetic patients from the National Health and Nutrition Examination Survey (NHANES), 1999 to 2018. Death outcomes were ascertained by linkage to National Death Index records through 31 December 2019. The Cox proportional-risk model was used to estimate hazard ratios (HR) and 95% CIs for mortality from all causes, CVD, and cancer. The mediating effects of 11 metabolic, cardiovascular, and renal biomarkers were evaluated using a logistic regression model within a counterfactual framework.

Results

During 8163 person-years of follow-up, 2310 deaths were documented, including 659 CVD deaths and 399 cancer deaths. After multivariate adjustment, lower serum bicarbonate levels were significantly linearly correlated with higher all-cause, CVD, and cancer mortality: The risk of all-cause death increased by 40%, the risk of CVD death increased by 48%, and the risk of cancer death increased by 84% compared with the normal group (all P < .05). Altered levels of estimated glomerular filtration rate explained 12.10% and 16.94% of the relation between serum bicarbonate with all-cause and CVD mortality, respectively. Total cholesterol mediated 4.70% and 10.51% of the associations of all-cause and CVD mortality, respectively.

Conclusion

Lower serum bicarbonate concentrations were significantly associated with higher all-cause, CVD, and cancer mortality. These findings suggest that maintaining adequate bicarbonate status may lower mortality risk in individuals with T2D.
Molecular basis for the recognition of the AUUAAA polyadenylation signal by mPSF
Authors: Gutierrez Pedro A. , Wei Jia , Sun Yadong , Tong Liang
Published: September 2022

The polyadenylation signal (PAS) is a key sequence element for 3′-end cleavage and polyadenylation of messenger RNA precursors (pre-mRNAs). This hexanucleotide motif is recognized by the mammalian polyadenylation specificity factor (mPSF), consisting of CPSF160, WDR33, CPSF30, and Fip1 subunits. Recent studies have revealed how the AAUAAA PAS, the most frequently observed PAS, is recognized by mPSF. We report here the structure of human mPSF in complex with the AUUAAA PAS, the second most frequently identified PAS. Conformational differences are observed for the A1 and U2 nucleotides in AUUAAA compared to the A1 and A2 nucleotides in AAUAAA, while the binding modes of the remaining 4 nt are essentially identical. The 5′ phosphate of U2 moves by 2.6 Å and the U2 base is placed near the six-membered ring of A2 in AAUAAA, where it makes two hydrogen bonds with zinc finger 2 (ZF2) of CPSF30, which undergoes conformational changes as well. We also attempted to determine the binding modes of two rare PAS hexamers, AAGAAA and GAUAAA, but did not observe the RNA in the cryo-electron microscopy density. The residues in CPSF30 (ZF2 and ZF3) and WDR33 that recognize PAS are disordered in these two structures.
Role of autonomous and endocrine factors in immunotropic effects of nitrogenous metabolites in patients with chronic pyelonephritis
Authors: Kuchma Igor , Korda Mykhaylo , Klishch Mykola , Popovych Dariya , Żukow Xawery , Popovych Igor
Published: September 2022

Background. We have previously shown that nitrogenous metabolites have immunomodulatory effects in healthy rats and humans as well as patients with dysfunction of neuroendocrine-immune complex, encephalopatia and chronic pyelonephritis. The purpose of this study is clarification of the role of neuro-endocrine factors in their immunotropic activity in patients with chronic pyelonephritis. Materials and Methods. The object of observation were 17 men (aged 24-70 years) with chronic pyelonephritis in remission. The plasma levels and urinary excretion of nitrogenous metabolites as well as parameters of immunity and its neuro-endocrine regulation twice (on admission and after balneotherapy at the Truskavets’ Spa) was performed. Results. Judging by the multiple correlation coefficient, uricosuria exhibits maximal neuro-endocrine activity (R=0,780), followed by bilirubinemia (R=0,742), creatinineuria (R=0,692), uricemia (R=0,636), creatinineemia (R=0,632), urea excretion (R=0,536), instead urea plasma correlate with neuro-endocrine parameters insignificantly (R=0,360). Nitrogenous metabolites together determine the state of neuro-endocrine regulation by 94,2%, which, in turn, determine the state of immunity by 99,9%. Conclusion. Nitrogenous metabolites carry out immunomodulation in different ways: directly through aryl hydrocarbon (bilirubin), toll-like and adenosine (uric acid) receptors of immunocytes; through modulation of the activity of neurons of the autonomous nervous system and endocrinocytes with subsequent neuro-endocrine immunomodulation; and also, apparently, due to an off-receptor effect on neurons, endocrinocytes and immunocytes (urea and creatinine).
Irritable bowel syndrome - pathophysiology, diagnosis, treatment. The role of low FODMAP diet
Authors: Gąbka Ilona , Dalmata Weronika , Dąbrowski Jan , Szarpak Julita , Lipiec Marta
Published: September 2022

Introduction: The gut microbiota is the microorganisms in the digestive tract. They are mainly bacteria. They play a very important role in maintaining the body's homeostasis. The state of the microbiota is influenced by lifestyle including diet, stress and physical activity. In irritable bowel syndrome, there are disorders in the composition of the intestinal microbiota. It is also associated with a disruption in the proper functioning of the gut-brain axis.    
Aim: The aim of this study was to review the literature reports on irritable bowel syndrome and the impact of a low FODMAP diet.
Methods:  Data for the article were retrieved using PubMed setting the time descriptors to 2017-2021.
Results and conclusions: Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disease. It is manifested by chronic abdominal pain , diarrhea or constipation and changes in the frequency of bowel movements. It significantly affects the quality of life of patients. The diagnosis uses the Roman IV criteria. Pharmacological as well as non-pharmacological methods are important in the treatment. A low-FODMAP diet plays a major role. Studies show that its proper use significantly alleviates the symptoms of IBS.
Therapeutic potential of Lion's Mane (Hericium erinaceus) in neurological and cognitive disorders - a review of the literature
Authors: Skubel Tomasz , Budzyńska Julia , Czarnota Jakub , Dobrzyński Michał , Rybak Natalia , Dudek Iga
Published: September 2022

Introduction:
Hericium erinaceus is a medicinal and culinary mushroom that is widely present in the countries of East Asia. Bioactive compounds derived from the fruiting body or its mycelium have many properties, including: antioxidant, antidiabetic, anti-inflammatory, as well as hypolipidemic properties. It also has the potential to treat neurological disorders as it contains neurotrophic compounds that can cross the blood-brain barrier.
Aim of the study: The aim of this work is to review scientific research on the potential properties of the H. erinaceus in treating diseases of the nervous system.
Results: Many studies have shown that Hericium erinaceus can bring the desired effects as a complementary treatment and be an alternative in the treatment of depressive and cognitive disorders and, due to its strong neuroprotective nature, be used in Alzheimer's disease or in post-traumatic brain injury. Most of the cited studies concern experiments carried out on animal models.
Conclusion: Due to the evidence of potentially neuroprotective properties of H. erinaceus, there is a need for further clinical trials in humans.
Raport. Pierwsza fala pandemii COVID-19 w Polsce: Ograniczenia i pomoc kierowana do przedsiębiorców
Authors: Koman Kacper , Syta Ziemowit
Published: September 2022

REPORT. THE FIRST WAVE OF THE COVID-19 PANDEMIC IN POLAND: RESTRICTIONS AND AID ADDRESSED TO ENTREPRENEURS The report presents a review of legal norms and a questionnaire study of the first wave of the COVID-19 pandemic in Poland (March to June 2020). The authors analysed legal regulations for four business industries: catering, tourism, transportation, and construction, both in terms of laws restricting the operation of these businesses due to the pandemic and aid regulations. The main objective of the research was to check whether the constitutionally established mechanism of determining the addressee’s relevant feature in formulating the aid solutions remains valid in the case of aid provided by the state to entrepreneurs affected by the pandemic crisis. The publication also contains observations and analyses concerning historical crises caused by forces of nature that occurred in Poland when the current Constitution was in force, and the methods of fighting the resulting damage at that time, with particular emphasis on the legal mechanisms that were applied in these situations. The summary of the report contains postulates of de lege ferenda character, whose introduction to the Polish legal order would result in a much higher than now level of preparedness of the state authorities for systemic, organised assistance in predefined forms to entities affected by natural disasters, with particular consideration of possible future events bearing traits of a pandemic.
Demodulation method based on a component synthesis and gradient projection for phase-shifting interferometry
Authors: Chen Yu , Zhong Ping , Zhang Bo , Zhu Jingfeng , Tang Xin , Du Shuai , Zheng Xinli
Published: September 2022

In order to reduce the vibration error of phase-shifting interferometry (PSI) and improve the demodulation accuracy of the wavefront phase, a demodulation method based on a component synthesis and gradient projection for PSI is proposed. For two sequences of interference images with a phase shift of 0,

π

/

2

, the method first corrects the vibration error by the pre-processing mechanism and multi-component synthesis. At the same time, two frames of interference images with a phase shift of 0,

π

/

2

are synthesized. Then the gradient projection algorithm is used to filter the background light of the synthesized image, and the wavefront phase is demodulated based on the arctangent operation. The experimental results show that the percentage of pixels demodulated effectively at the truncated interface is more than 90%. Compared with the traditional demodulation method, the number of pixels demodulated effectively (demodulation accuracy) is improved.
EpiBeds: Data informed modelling of the COVID-19 hospital burden in England
Authors: Overton Christopher E. , Pellis Lorenzo , Stage Helena B. , Scarabel Francesca , Burton Joshua , Fraser Christophe , Hall Ian , House Thomas A. , Jewell Chris , Nurtay Anel , Pagani Filippo , Lythgoe Katrina A.
Published: September 2022

The first year of the COVID-19 pandemic put considerable strain on healthcare systems worldwide. In order to predict the effect of the local epidemic on hospital capacity in England, we used a variety of data streams to inform the construction and parameterisation of a hospital progression model, EpiBeds, which was coupled to a model of the generalised epidemic. In this model, individuals progress through different pathways (e.g. may recover, die, or progress to intensive care and recover or die) and data from a partially complete patient-pathway line-list was used to provide initial estimates of the mean duration that individuals spend in the different hospital compartments. We then fitted EpiBeds using complete data on hospital occupancy and hospital deaths, enabling estimation of the proportion of individuals that follow the different clinical pathways, the reproduction number of the generalised epidemic, and to make short-term predictions of hospital bed demand. The construction of EpiBeds makes it straightforward to adapt to different patient pathways and settings beyond England. As part of the UK response to the pandemic, EpiBeds provided weekly forecasts to the NHS for hospital bed occupancy and admissions in England, Wales, Scotland, and Northern Ireland at national and regional scales.
Probing the rules of cell coordination in live tissues by interpretable machine learning based on graph neural networks
Authors: Yamamoto Takaki , Cockburn Katie , Greco Valentina , Kawaguchi Kyogo
Published: September 2022

Robustness in developing and homeostatic tissues is supported by various types of spatiotemporal cell-to-cell interactions. Although live imaging and cell tracking are powerful in providing direct evidence of cell coordination rules, extracting and comparing these rules across many tissues with potentially different length and timescales of coordination requires a versatile framework of analysis. Here we demonstrate that graph neural network (GNN) models are suited for this purpose, by showing how they can be applied to predict cell fate in tissues and utilized to infer the cell interactions governing the multicellular dynamics. Analyzing the live mammalian epidermis data, where spatiotemporal graphs constructed from cell tracks and cell contacts are given as inputs, GNN discovers distinct neighbor cell fate coordination rules that depend on the region of the body. This approach demonstrates how the GNN framework is powerful in inferring general cell interaction rules from live data without prior knowledge of the signaling involved.
Role of the reaction-structure coupling in temperature compensation of the KaiABC circadian rhythm
Authors: Sasai Masaki
Published: September 2022

When the mixture solution of cyanobacterial proteins, KaiA, KaiB, and KaiC, is incubated with ATP in vitro, the phosphorylation level of KaiC shows stable oscillations with the temperature-compensated circadian period. Elucidating this temperature compensation is essential for understanding the KaiABC circadian clock, but its mechanism has remained a mystery. We analyzed the KaiABC temperature compensation by developing a theoretical model describing the feedback relations among reactions and structural transitions in the KaiC molecule. The model showed that the reduced structural cooperativity should weaken the negative feedback coupling among reactions and structural transitions, which enlarges the oscillation amplitude and period, explaining the observed significant period extension upon single amino-acid residue substitution. We propose that an increase in thermal fluctuations similarly attenuates the reaction-structure feedback, explaining the temperature compensation in the KaiABC clock. The model explained the experimentally observed responses of the oscillation phase to the temperature shift or the ADP-concentration change and suggested that the ATPase reactions in the CI domain of KaiC affect the period depending on how the reaction rates are modulated. The KaiABC clock provides a unique opportunity to analyze how the reaction-structure coupling regulates the system-level synchronized oscillations of molecules.
A bipartite, low-affinity roadblock domain-containing GAP complex regulates bacterial front-rear polarity
Authors: Szadkowski Dobromir , Carreira Luís António Menezes , Søgaard-Andersen Lotte
Published: September 2022

The Ras-like GTPase MglA is a key regulator of front-rear polarity in the rod-shaped Myxococcus xanthus cells. MglA-GTP localizes to the leading cell pole and stimulates assembly of the two machineries for type IV pili-dependent motility and gliding motility. MglA-GTP localization is spatially constrained by its cognate GEF, the RomR/RomX complex, and GAP, the MglB Roadblock-domain protein. Paradoxically, RomR/RomX and MglB localize similarly with low and high concentrations at the leading and lagging poles, respectively. Yet, GEF activity dominates at the leading and GAP activity at the lagging pole by unknown mechanisms. Here, we identify RomY and show that it stimulates MglB GAP activity. The MglB/RomY interaction is low affinity, restricting formation of the bipartite MglB/RomY GAP complex almost exclusively to the lagging pole with the high MglB concentration. Our data support a model wherein RomY, by forming a low-affinity complex with MglB, ensures that the high MglB/RomY GAP activity is confined to the lagging pole where it dominates and outcompetes the GEF activity of the RomR/RomX complex. Thereby, MglA-GTP localization is constrained to the leading pole establishing front-rear polarity.
Strongyloides stercoralis infection induces gut dysbiosis in chronic kidney disease patients
Authors: Hai Nguyen Thi , Hongsrichan Nuttanan , Intuyod Kitti , Pinlaor Porntip , Yingklang Manachai , Chaidee Apisit , Pongking Thatsanapong , Anutrakulchai Sirirat , Cha’on Ubon , Pinlaor Somchai
Published: September 2022

Background

Strongyloides stercoralis infection typically causes severe symptoms in immunocompromised patients. This infection can also alter the gut microbiota and is often found in areas where chronic kidney disease (CKD) is common. However, the relationship between S. stercoralis and the gut microbiome in chronic kidney disease (CKD) is not understood fully. Recent studies have shown that gut dysbiosis plays an important role in the progression of CKD. Hence, this study aims to investigate the association of S. stercoralis infection and gut microbiome in CKD patients.

Methodology/Principal findings

Among 838 volunteers from Khon Kaen Province, northeastern Thailand, 40 subjects with CKD were enrolled and divided into two groups (S. stercoralis-infected and -uninfected) matched for age, sex and biochemical parameters. Next-generation technology was used to amplify and sequence the V3-V4 region of the 16S rRNA gene to provide a profile of the gut microbiota. Results revealed that members of the S. stercoralis-infected group had lower gut microbial diversity than was seen in the uninfected group. Interestingly, there was significantly greater representation of some pathogenic bacteria in the S. stercoralis-infected CKD group, including Escherichia-Shigella (P = 0.013), Rothia (P = 0.013) and Aggregatibacter (P = 0.03). There was also a trend towards increased Actinomyces, Streptococcus and Haemophilus (P > 0.05) in this group. On the other hand, the S. stercoralis-infected CKD group had significantly lower representation of SCFA-producing bacteria such as Anaerostipes (P = 0.01), Coprococcus_1 (0.043) and a non-significant decrease of Akkermansia, Eubacterium rectale and Eubacterium hallii (P > 0.05) relative to the uninfected group. Interesting, the genera Escherichia-Shigella and Anaerostipes exhibited opposing trends, which were significantly related to sex, age, infection status and CKD stages. The genus Escherichia-Shigella was significantly more abundant in CKD patients over the age of 65 years and infected with S. stercoralis. A correlation analysis showed inverse moderate correlation between the abundance of the genus of Escherichia-Shigella and the level of estimated glomerular filtration rate (eGFR).

Conclusions/Significance

Conclusion, the results suggest that S. stercoralis infection induced gut dysbiosis in the CKD patients, which might be involved in CKD progression.
Development, feasibility and potential effectiveness of community-based continuous mass dog vaccination delivery strategies: Lessons for optimization and replication
Authors: Duamor Christian Tetteh , Hampson Katie , Lankester Felix , Lugelo Ahmed , Mpolya Emmanuel , Kreppel Katharina , Cleaveland Sarah , Wyke Sally
Published: September 2022

Objectives

Dog vaccination can eliminate rabies in dogs, but annual delivery strategies do not sustain vaccination coverage between campaigns. We describe the development of a community-based continuous mass dog vaccination (CBC-MDV) approach designed to improve and maintain vaccination coverage in Tanzania and examine the feasibility of delivering this approach as well as lessons for its optimization.

Methods

We developed three delivery strategies of CBC-MDV and tested them against the current annual vaccination strategy following the UK Medical Research Council’s guidance: i) developing an evidence-based theoretical framework of intervention pathways and ii) piloting to test feasibility and inform optimization. For our process evaluation of CBC-MDV we collected data using non-participant observations, meeting reports and implementation audits and in-depth interviews, as well as household surveys of vaccination coverage to assess potential effectiveness. We analyzed qualitative data thematically and quantitative data descriptively.

Results

The final design included delivery by veterinary teams supported by village-level one health champions. In terms of feasibility, we found that less than half of CBC-MDV’s components were implemented as planned. Fidelity of delivery was influenced by the strategy design, implementer availability and appreciation of value intervention components, and local environmental and socioeconomic events (e.g. elections, funerals, school cycles). CBC-MDV activities decreased sharply after initial campaigns, partly due to lack of supervision. Community engagement and involvement was not strong. Nonetheless, the CBC-MDV approaches achieved vaccination coverage above the critical threshold (40%) all-year-round. CBC-MDV components such as identifying vaccinated dogs, which village members work as one health champions and how provision of continuous vaccination is implemented need further optimization prior to scale up.

Interpretation

CBC-MDV is feasible to deliver and can achieve good vaccination coverage. Community involvement in the development of CBC-MDV, to better tailor components to contextual situations, and improved supervision of activities are likely to improve vaccination coverage in future.
Delayed detection of leprosy cases: A systematic review of healthcare-related factors
Authors: Dharmawan Yudhy , Fuady Ahmad , Korfage Ida J. , Richardus Jan Hendrik
Published: September 2022

Background

In new leprosy cases, grade 2 disability (G2D) is still a public health burden worldwide. It is often associated with the delayed leprosy diagnoses that healthcare systems should play a crucial role in preventing. The aim of this systematic review was to identify healthcare factors related to delays in case detection in leprosy.

Methods

PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) was used as a guideline in this research. The study protocol was registered in the PROSPERO (International Prospective Register of Systematic Reviews) with reference code CRD42020189274. Data was collected from five electronic databases: Embase, Medline All Ovid, Web of Science, Cochrane CENTRAL, and the WHO Global Health Library.

Results

After applying the selection criteria for original empirical studies, and after removing duplicates, we included 20 papers from 4313 records. They had been conducted in ten countries and published between January 1, 2000, and January 31, 2021. We identified three categories of healthcare factors related to delayed case. 1) Structural factors, such as i) financial and logistic issues, and geographical circumstances (which we classified as barriers); ii) Health service organization and management including the level of decentralization (classified as facilitators). 2) Health service factors, such as problems or shortages involving referral centers, healthcare personnel, and case-detection methods. 3) Intermediate factors, such as misdiagnosis, higher numbers of consultations before diagnosis, and inappropriate healthcare services visited by people with leprosy.

Conclusions

Delays in leprosy case detection are due mainly to misdiagnosis. It is crucial to improve the training and capacity of healthcare staff. To avoid misdiagnosis and reduce detection delays, national leprosy control programs should ensure the sustainability of leprosy control within integrated health services.
Spatially resolved characterization of tissue metabolic compartments in fasted and high-fat diet livers
Authors: Stopka Sylwia A. , van der Reest Jiska , Abdelmoula Walid M. , Ruiz Daniela F. , Joshi Shakchhi , Ringel Alison E. , Haigis Marcia C. , Agar Nathalie Y. R.
Published: September 2022

Cells adapt their metabolism to physiological stimuli, and metabolic heterogeneity exists between cell types, within tissues, and subcellular compartments. The liver plays an essential role in maintaining whole-body metabolic homeostasis and is structurally defined by metabolic zones. These zones are well-understood on the transcriptomic level, but have not been comprehensively characterized on the metabolomic level. Mass spectrometry imaging (MSI) can be used to map hundreds of metabolites directly from a tissue section, offering an important advance to investigate metabolic heterogeneity in tissues compared to extraction-based metabolomics methods that analyze tissue metabolite profiles in bulk. We established a workflow for the preparation of tissue specimens for matrix-assisted laser desorption/ionization (MALDI) MSI that can be implemented to achieve broad coverage of central carbon, nucleotide, and lipid metabolism pathways. Herein, we used this approach to visualize the effect of nutrient stress and excess on liver metabolism. Our data revealed a highly organized metabolic tissue compartmentalization in livers, which becomes disrupted under high fat diet. Fasting caused changes in the abundance of several metabolites, including increased levels of fatty acids and TCA intermediates while fatty livers had higher levels of purine and pentose phosphate-related metabolites, which generate reducing equivalents to counteract oxidative stress. This spatially conserved approach allowed the visualization of liver metabolic compartmentalization at 30 μm pixel resolution and can be applied more broadly to yield new insights into metabolic heterogeneity in vivo.
Optimization of technique parameters of pneumatic molding for rice straw bowl tray
Authors: Li Hailiang , Wang Chun , Sun Haitian , Zou Huafen , Wang Hongxuan , Wang Huiyuan , Liu Xinyu , Yu Zhenzhen
Published: September 2022

In order to find out the optimized technological parameters of rice straw bowl tray, the forming test was carried out with the slurry made of rice straw as the main raw material and the pneumatic molding machine as the equipment. The orthogonal rotational combination test of ternary quadratic regression and response surface analysis method were used to study the effect of 3 molding factors (vacuum degree, pressure preservation time and adsorption time) on 3 molding technical indices (bowl hole molding rate, relaxation density and rupture-resisting strength). Design-Expert data analysis software was used to establish regression models between rice straw bowl tray molding factors and molding properties so as to obtain optimal technological parameters, which were as follows: vacuum degree: -0.09 MPa; holding time: 14 s; adsorption time: 5 s. At the moment, theoretical bowl hole molding rate was 98.62%, relaxation density was 5.8 g/cm3 and rupture-resisting strength was 27.48 N, the experimental results show that the theoretical analysis is correct, and the model fitting is better. This study can provide a theoretical basis for optimization of pneumatic molding technological of rice straw bowl tray and lay a foundation for realizing industrialized production of biomass seeding tray.
Detection of human feces pecovirus in newly diagnosed HIV patients in Brazil
Authors: Sanz Duro Rodrigo Lopes , Marinho Robson dos Santos Souza , Santana Valquíria Lima , Monti Elis Muriel Marques , Onias Humberto , Matsuda Elaine Monteiro , Diaz Ricardo Sobhie , Isidoro Karina Rente , Delwart Eric , Leal Élcio , Komninakis Shirley Vasconcelos
Published: September 2022

Circular single stranded DNA viruses (CRESS DNA) encoding a homologous replication-associated protein (REP) have been identified in most of eukaryotic groups. It is not clear yet the role in human diseases or details of the life cycle of these viruses. Recently, much interest has been raised in the evolutionary history of CRESS DNA owing to the increasing number of new sequences obtained by Next-Generation Sequencing (NGS) in distinct host species. In this study we describe two full-length CRESS DNA genomes obtained of two newly diagnosed HIV patients from São Paulo State, Brazil. The initial BLASTx search indicated that both sequences (named SP-FFB/2020 and SP-MJMS/2020) are highly similar (98%) to a previous CRESS DNA sequence detected in human fecal sample from Peru in 2016 and designated as pecovirus (Peruvian stool-associated circo-like virus). This study reported for the first time the Human feces pecovirus in the feces of two newly diagnosed HIV patients in Brazil. Our comparative analysis showed that although pecoviruses in South America share an identical genome structure they diverge and form distinct clades. Thus, we suggest the circulation of different species of pecoviruses in Latin America. Nevertheless, further studies must be done to examine the pathogenicity of this virus.