bluuebunny/crossref_metadata_2025 huggingface dataset:
Metatranscriptomic assessment of diarrhoeic faeces reveals diverse RNA viruses in rotavirus group A infected piglets and calves from India
Authors: Sawant Pradeep , Kulkarni Abhijeet , Mane Rajkumar , Patil Renu , Lavania Mallika
Published: October 2023

RNA viruses are a major group contributing to emerging infectious diseases and neonatal diarrhoea, causing morbidity and mortality in humans and animals. Hence, the present study investigated the metatranscriptomic-derived faecal RNA virome in rotavirus group A (RVA)-infected diarrheic piglets and calves from India. The viral genomes retrieved belonged to Astroviridae in both species, while Reoviridae and Picornaviridae were found only in piglets. The nearly complete genomes of porcine RVA (2), astrovirus (AstV) (6), enterovirus G (EVG) (2), porcine sapelovirus (PSV) (2), Aichivirus C (1), and porcine teschovirus (PTV) (1) were identified and characterised. In the piglet, AstVs of PAstV2 (MAstV-26) and PAstV4 (MAstV-31) lineages were predominant, followed by porcine RVA, EVG, PSV, Aichivirus C, teschovirus (PTV-17) in decreasing order of sequence reads. In contrast, AstV accounted for the majority of reads in bovines and belonged to MAstV-28 and a proposed MAstV-35. Both RVA G4P[6] strains exhibited prototype Gottfried strains like a genotypic constellation of G4-P[6]-I1-R1-C1-M1-A8-N1-T1-E1-H1. Ten out of eleven genes were of porcine origin, while the VP7 gene clustered with G4-lineage-1, consisting of human strains, suggesting a natural porcine-human reassortant. In the recombination analysis, multiple recombination events were detected in the PAstV4 and PAstV2 genomes, pointing out that these viruses were potential recombinants. Finally, the study finds diverse RNA virome in Indian piglets and calves for the first time, which may have contributed to diarrhoea. In the future, the investigation of RNA virome in animals will help in revealing pathogen diversity in multifactorial diseases, disease outbreaks, monitoring circulating viruses, viral discovery, and evaluation of their zoonotic potential.
Novel NKG2D-directed bispecific antibodies enhance antibody-mediated killing of malignant B cells by NK cells and T cells
Authors: Lutz Sebastian , Klausz Katja , Albici Anca-Maria , Ebinger Lea , Sellmer Lea , Teipel Hannah , Frenzel André , Langner Anna , Winterberg Dorothee , Krohn Steffen , Hust Michael , Schirrmann Thomas , Dübel Stefan , Scherließ Regina , Humpe Andreas , Gramatzki Martin , Kellner Christian , Peipp Matthias
Published: October 2023

The activating receptor natural killer group 2, member D (NKG2D) represents an attractive target for immunotherapy as it exerts a crucial role in cancer immunosurveillance by regulating the activity of cytotoxic lymphocytes. In this study, a panel of novel NKG2D-specific single-chain fragments variable (scFv) were isolated from naïve human antibody gene libraries and fused to the fragment antigen binding (Fab) of rituximab to obtain [CD20×NKG2D] bibodies with the aim to recruit cytotoxic lymphocytes to lymphoma cells. All bispecific antibodies bound both antigens simultaneously. Two bibody constructs, [CD20×NKG2D#3] and [CD20×NKG2D#32], efficiently activated natural killer (NK) cells in co-cultures with CD20+ lymphoma cells. Both bibodies triggered NK cell-mediated lysis of lymphoma cells and especially enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) by CD38 or CD19 specific monoclonal antibodies suggesting a synergistic effect between NKG2D and FcγRIIIA signaling pathways in NK cell activation. The [CD20×NKG2D] bibodies were not effective in redirecting CD8+ T cells as single agents, but enhanced cytotoxicity when combined with a bispecific [CD19×CD3] T cell engager, indicating that NKG2D signaling also supports CD3-mediated T cell activation. In conclusion, engagement of NKG2D with bispecific antibodies is attractive to directly activate cytotoxic lymphocytes or to support their activation by monoclonal antibodies or bispecific T cell engagers. As a perspective, co-targeting of two tumor antigens may allow fine-tuning of antibody cancer therapies. Our proposed combinatorial approach is potentially applicable for many existing immunotherapies but further testing in different preclinical models is necessary to explore the full potential.
A direct contact pig influenza challenge model for assessing protective efficacy of monoclonal antibodies
Authors: McNee Adam , Vanover Daryll , Rijal Pramila , Paudyal Basudev , Lean Fabian Z. X. , MacLoughlin Ronan , Núñez Alejandro , Townsend Alain , Santangelo Philip J. , Tchilian Elma
Published: October 2023

Monoclonal antibodies (mAbs) can be used to complement immunization for the therapy of influenza virus infection. We have established the pig, a natural large animal host for influenza A, with many physiological, immunological, and anatomical similarities to humans, as an appropriate model for testing mAbs. We have evaluated the protective efficacy of the strongly neutralizing human anti-hemagglutinin mAb, 2-12C in the pig influenza model. Intravenous administration of recombinant 2-12C reduced virus load and lung pathology, however, it did not prevent virus nasal shedding and, consequently, transmission. This may be because the pigs were directly infected intranasally with a high dose of the H1N1pdm09 virus. To address this, we developed a contact challenge model in which the animals were given 2-12C and one day later co-housed with donor pigs previously infected intra-nasally with H1N1pdm09. 2-12C pre-treatment completely prevented infection. We also administered a lower dose of 2-12C by aerosol to the respiratory tract, but this did not prevent shedding in the direct challenge model, although it abolished lung infection. We propose that the direct contact challenge model of pig influenza may be useful for evaluating candidate mAbs and emerging delivery platforms prior to clinical trials.
SpiB regulates the expression of B-cell-related genes and increases the longevity of memory B cells
Authors: Horiuchi Shu , Koike Takuya , Takebuchi Hirofumi , Hoshino Katsuaki , Sasaki Izumi , Fukuda-Ohta Yuri , Kaisho Tsuneyasu , Kitamura Daisuke
Published: October 2023

Generation of memory B cells is one of the key features of adaptive immunity as they respond rapidly to re-exposure to the antigen and generate functional antibodies. Although the functions of memory B cells are becoming clearer, the regulation of memory B cell generation and maintenance is still not well understood. Here we found that transcription factor SpiB is expressed in some germinal center (GC) B cells and memory B cells and participates in the maintenance of memory B cells. Overexpression and knockdown analyses revealed that SpiB suppresses plasma cell differentiation by suppressing the expression of Blimp1 while inducing Bach2 in the in-vitro-induced germinal center B (iGB) cell culture system, and that SpiB facilitates in-vivo appearance of memory-like B cells derived from the iGB cells. Further analysis in IgG1+ cell-specific SpiB conditional knockout (cKO) mice showed that function of SpiB is critical for the generation of late memory B cells but not early memory B cells or GC B cells. Gene expression analysis suggested that SpiB-dependent suppression of plasma cell differentiation is independent of the expression of Bach2. We further revealed that SpiB upregulates anti-apoptosis and autophagy genes to control the survival of memory B cells. These findings indicate the function of SpiB in the generation of long-lasting memory B cells to maintain humoral memory.
IFN-γ lowers tumor growth by increasing glycolysis and lactate production in a nitric oxide-dependent manner: implications for cancer immunotherapy
Authors: Chattopadhyay Avik , Jagdish Sirisha , Karhale Aagosh Kishor , Ramteke Nikita S. , Zaib Arsha , Nandi Dipankar
Published: October 2023

Introduction

Interferon-gamma (IFN-γ), the sole member of the type-II interferon family, is well known to protect the host from infectious diseases as well as mount anti-tumor responses. The amounts of IFN-γ in the tumor microenvironment determine the host responses against tumors; however, several tumors employ evasive strategies by responding to low IFN-γ signaling.

Methods

In this study, the response of various tumor cell lines to IFN-γ was studied in vitro.

Results

IFN-γ-activation increases glycolytic flux and reduces mitochondrial function in a nitric oxide (NO)- and reactive oxygen species (ROS)-dependent manner in the H6 hepatoma tumor cell line. The higher glycolysis further fueled NO and ROS production, indicating a reciprocal regulation. These processes are accompanied by Hypoxia inducing factor (HIF)-1α stabilization and HIF-1α-dependent augmentation of the glycolytic flux. The IFN-γ enhancement of lactate production also occurred in other NO-producing cell lines: RAW 264.7 monocyte/macrophage and Renca renal adenocarcinoma. However, two other tumor cell lines, CT26 colon carcinoma and B16F10 melanoma, did not produce NO and lactate upon IFN-γ-activation. HIF-1α stabilization upon IFN-γ-activation led to lower cell growth of B16F10 but not CT26 cells. Importantly, the IFN-γ-activation of both CT26 and B16F10 cells demonstrated significant cellular growth reduction upon metabolic rewiring by exogenous administration of potassium lactate.

Discussion

Clinical studies have shown the crucial roles of IFN-γ for successful cancer immunotherapies involving checkpoint inhibitors and chimeric antigen receptor T cells. The positive implications of this study on the metabolic modulation of IFN-γ activation on heterogeneous tumor cells are discussed.
Quantitative electroencephalography predicts postoperative delirium in cardiac surgical patients after cardiopulmonary bypass: a prospective observational study
Authors: Xue Yuechuan , Liu Wanglin , Su Longxiang , He Huaiwu , Chen Huan , Long Yun
Published: October 2023

Objective

Despite its frequency and associated negative effect, delirium remains poorly recognized in postoperative patients after ICU admission, especially among those who have undergone cardiac surgery with cardiopulmonary bypass. Postoperative delirium is triggered by a wide variety of acute medical conditions associated with impaired neuronal network connectivity. The lack of objective biomarkers primarily hinders the early detection of delirium. Seeking early biomarkers for tracking POD could potentially assist in predicting the onset of delirium and assessing the severity of delirium and response to interventions.

Methods

QEEGs were taken from 46 sedated postoperative patients, with 24 of them having undergone cardiac surgery. The assessment of delirium was performed twice daily using the Confusion Assessment Method for the ICU (CAM-ICU) to screen for postoperative delirium (POD). QEEG data were interpreted clinically by neurophysiologists and processed by open-source EEGLAB to identify features in patients who had or did not have POD after cardiac or non-cardiac surgery.

Results

The incidence of delirium in patients after undergoing cardiac surgery was nine times greater than in those after non-cardiac surgeries (41.7% vs. 4.5%; p = 0.0046). Patients with delirium experienced longer use of mechanical ventilation (118 h (78,323) compared to 20 h (18,23); p < 0.0001) and an extended ICU length of stay (7 days (6, 20) vs. 2 days (2, 4); p < 0.0001). The depth of anesthesia, as measured by RASS scores (p = 0.3114) and spectral entropy (p = 0.1504), showed no significant difference. However, notable differences were observed between delirious and non-delirious patients in terms of the amplitude-integrated EEG (aEEG) upper limit, the relative power of the delta band, and spectral edge frequency 95 (SEF95) (p = 0.0464, p = 0.0417, p = 0.0337, respectively).

Conclusion

In a homogenous population of sedated postoperative patients, robust qEEG parameters strongly correlate with delirium and could serve as valuable biomarkers for early detection of delirium and assist in clinical decision-making.
Amerindian ancestry proportion as a risk factor for inflammatory bowel diseases: results from a Latin American Andean cohort
Authors: Pérez-Jeldres Tamara , Magne Fabien , Ascui Gabriel , Alvares Danilo , Orellana Matias , Alvarez-Lobos Manuel , Hernandez-Rocha Cristian , Azocar Lorena , Aguilar Nataly , Espino Alberto , Estela Ricardo , Escobar Sergio , Zazueta Alejandra , Baez Pablo , Silva Verónica , De La Vega Andres , Arriagada Elizabeth , Pavez-Ovalle Carolina , Díaz-Asencio Alejandro , Travisany Dante , Miquel Juan Francisco , Villablanca Eduardo J. , Kronenberg Mitchell , Bustamante María Leonor
Published: October 2023

Background and aims

Latin American populations remain underrepresented in genetic studies of inflammatory bowel diseases (IBDs). Most genetic association studies of IBD rely on Caucasian, African, and Asian individuals. These associations have yet to be evaluated in detail in the Andean region of South America. We explored the contribution of IBD-reported genetic risk variants to a Chilean cohort and the ancestry contribution to IBD in this cohort.

Methods

A total of 192 Chilean IBD patients were genotyped using Illumina's Global Screening Array. Genotype data were combined with similar information from 3,147 Chilean controls. The proportions of Aymara, African, European, and Mapuche ancestries were estimated using the software ADMIXTURE. We calculated the odds ratios (ORs) and 95% confidence intervals (CIs) for gender, age, and ancestry proportions. We also explored associations with previously reported IBD-risk variants independently and in conjunction with genetic ancestry.

Results

The first and third quartiles of the proportion of Mapuche ancestry in IBD patients were 24.7 and 34.2%, respectively, and the corresponding OR was 2.30 (95%CI 1.52–3.48) for the lowest vs. the highest group. Only one variant (rs7210086) of the 180 reported IBD-risk SNPs was associated with IBD risk in the Chilean cohort (adjusted P = 0.01). This variant is related to myeloid cells.

Conclusion

The type and proportion of Native American ancestry in Chileans seem to be associated with IBD risk. Variants associated with IBD risk in this Andean region were related to myeloid cells and the innate immune response.
A study on the normative path of ethics review in China: based on the perspective of Panopticism
Authors: Wu Leqian , Kong Xiangjin
Published: October 2023

Modern biomedical technology is in an era of dramatic development, which brings unprecedented challenges to the work of ethics review and provides a turning point for the construction of ethics review system. The current ethics review committee (ERC) in China is executed with low efficiency and quality, which can hardly meet the current needs of biomedical research involving human beings. This paper summarizes the main connotations and roles of the sign system technique and the discipline mechanism through the idea of Foucault’s Panopticism, and proposes to incorporate the Panopticism into the construction of the ethics review system and establish the sign system and discipline mechanism of ethics review, in order to build an ethics review system and the operation system of the ethics review committee suitable for China’s national conditions.
The signaling pathway of hypoxia inducible factor in regulating gut homeostasis
Authors: Liu Wei , Fan Xueni , Jian Boshuo , Wen Dongxu , Wang Hongzhuang , Liu Zhenjiang , Li Bin
Published: October 2023

Hypoxia represent a condition in which an adequate amount of oxygen supply is missing in the body, and it could be caused by a variety of diseases, including gastrointestinal disorders. This review is focused on the role of hypoxia in the maintenance of the gut homeostasis and related treatment of gastrointestinal disorders. The effects of hypoxia on the gut microbiome and its role on the intestinal barrier functionality are also covered, together with the potential role of hypoxia in the development of gastrointestinal disorders, including inflammatory bowel disease and irritable bowel syndrome. Finally, we discussed the potential of hypoxia-targeted interventions as a novel therapeutic approach for gastrointestinal disorders. In this review, we highlighted the importance of hypoxia in the maintenance of the gut homeostasis and the potential implications for the treatment of gastrointestinal disorders.
Adequacy of iodized salt and its associated factors among households in the Bahir Dar Zuria district, Northwest Ethiopia, 2022
Authors: Temech Emebet Chalachew , Said Oumer , Endalik Genete , Demilew Yeshalem Mulugeta , Belay Mahider Awoke , Kassie Tadele Derbew , Dessie Anteneh Mengist
Published: October 2023

Background

The inadequacy of iodine in salt is the a contributing factor behind lack of awareness and poor economic performance in developing countries. To address the issue of iodine deficiency, universal salt iodization has been implemented globally. Nevertheless, it is imperative to closely monitor the sufficiency of iodine in salts to achieve its intended objective at the household level in the Bahir Dar Zuria district.

Objective

To assess the adequacy of iodized salt and its associated factors among households in the Bahir Dar Zuria district, Northwest Ethiopia.

Methods

A community-based cross-sectional study was conducted from May to June 2022 among households in Bahir Dar Zuria district. The data were gathered from 825 households that were chosen using a multistage sampling process. Iodometric titration was used to assess the amount of iodine in salt. The data were gathered using a structured questionnaire that was administered by an interviewer. For data entry and analysis, EpiData version 3.01 and SPSS version 25.0 were used, respectively. To evaluate the association between explanatory factors and the outcome variable, binary logistic regression was conducted, and significance was determined at alpha 0.05.

Result

This study analyzed a total of 825 households. Of these, only 384 [46.5, 95% CI, 43.5–50.5%] households had adequately iodized salt at home. Age increase of 1 year [AOR = 1.04, 95% CI = 1.02–1.06], being an urban resident [AOR = 3.18, 95% CI = 1.84–5.48], diploma and above educational attainment [AOR = 3.74, 95% CI = 1.99–7.02], checking salt by asking the seller [AOR = 2.21, 95% CI = 1.26–3.88], storing salts in closed containers [AOR = 1.57, 95% CI = 1.13–2.19], and storing salts in a dry and cool area [AOR = 2.72, 95% CI =1.37–5.42] were associated with the adequacy of iodized salt at the household level.

Conclusion and recommendation

The percentage of households in the district (46.5%) that had enough iodized salt in their homes is still extremely low and falls short of the targeted level for the country. At the household level, adequate iodized salt was found to be associated with age, place of residence, level of education, checking salt iodization while purchasing, place of salt storage, and cover use for salt containers. Therefore, increasing the accessibility of iodized salt at the household level is essential.
Cluster headache: state of the art in treatment
Authors: Rodriguez-Leyva Ildefonso , Velez-Jimenez Maria-Karina , García Silvia , Nader-Kawachi Juan Alberto , Martínez-Mayorga Adriana Patricia , Melo-Carrillo Agustín , Juárez-Jimenez Humberto , Martinez-Gurrola Marco , Gudiño-Castelazo Manuel , Chiquete Erwin , Villareal-Careaga Jorge , Marfil Alejandro , Uribe-Jaimes Paul David , Vargas-García Rubén Dario , Collado-Ortiz Miguel Angel , San-Juan Daniel
Published: October 2023

Cluster headache (CH) is the most common and devastating autonomic headache with multiple and recent advances in treatment. However, it usually goes unrecognized and is found to have a delayed and inappropriate treatment. This paper aims to review the current therapeutic options for patients with CH. We conducted a narrative literature review on the treatments available for this condition using the American Academy of Neurology (AAN) classification of therapeutic evidence. We found effective and safe pharmacological and non-pharmacological therapies with heterogeneity of clinical trial designs for patients with CH, and they are divided into three phases, namely, transitional, acute, and preventive interventions. Prednisone (A) is the most studied treatment in the transitional phase; acute attacks are treated using triptans (A), oxygen (A), and non-invasive transcutaneous vagal nerve stimulation (A). Verapamil (A) and monoclonal antibodies (possible A) are considered the first options in preventive treatments, followed by multiple pharmacological and non-pharmacological options in prophylactic treatments. In conclusion, numerous effective and safe treatments are available in treating patients with episodic, chronic, and pharmacoresistant CH according to the clinical profile of each patient.
A systematic review and activation likelihood estimation meta-analysis of fMRI studies on arousing or wake-promoting effects in Buddhist meditation
Authors: Chaudhary Inder S. , Shyi Gary Chon-Wen , Huang Shih-Tseng Tina
Published: October 2023

Conventional Buddhist texts illustrate meditation as a condition of relaxed alertness that must fend against extreme hypoarousal (sleep, drowsiness) and extreme hyperarousal (restlessness). Theoretical, neurophysiological, and neuroimaging investigations of meditation have highlighted the relaxing effects and hypoarousing without emphasizing the alertness-promoting effects. Here we performed a systematic review supported by an activation-likelihood estimate (ALE) meta-analysis in an effort to counterbalance the surfeit of scholarship emphasizing the hypoarousing and relaxing effects of different forms of Buddhist meditation. Specifically, the current systematic review-cum-meta-analytical review seeks to highlight more support for meditation’s wake-promoting effects by drawing from neuroimaging research during wakefulness and meditation. In this systematic review and meta-analysis of 22 fMRI studies, we aim to highlight support for Buddhist meditation’s wake-promoting or arousing effects by identifying brain regions associated with alertness during meditation. The most significant peaks were localized medial frontal gyrus (MFG) and precuneus. We failed to determine areas ostensibly common to alertness-related meditation such as the medial prefrontal cortex (mPFC), superior parietal lobule, basal ganglia, thalamus, most likely due to the relatively fewer fMRI investigations that used wakefulness-promoting meditation techniques. Also, we argue that forthcoming research on meditation, related to alertness or wakefulness, continues to adopt a multi-modal method to investigate the correlation between actual behaviors and neural networks connected to Buddhist meditation. Moreover, we recommend the implementation of fMRI paradigms on Buddhist meditation with clinically diagnosed participants to complement recent trends in psychotherapy such as mindfulness-based cognitive therapy (MBCT).
An evidence-based critical review of the mind-brain identity theory
Authors: Masi Marco
Published: October 2023

In the philosophy of mind, neuroscience, and psychology, the causal relationship between phenomenal consciousness, mentation, and brain states has always been a matter of debate. On the one hand, material monism posits consciousness and mind as pure brain epiphenomena. One of its most stringent lines of reasoning relies on a ‘loss-of-function lesion premise,’ according to which, since brain lesions and neurochemical modifications lead to cognitive impairment and/or altered states of consciousness, there is no reason to doubt the mind-brain identity. On the other hand, dualism or idealism (in one form or another) regard consciousness and mind as something other than the sole product of cerebral activity pointing at the ineffable, undefinable, and seemingly unphysical nature of our subjective qualitative experiences and its related mental dimension. Here, several neuroscientific findings are reviewed that question the idea that posits phenomenal experience as an emergent property of brain activity, and argue that the premise of material monism is based on a logical correlation-causation fallacy. While these (mostly ignored) findings, if considered separately from each other, could, in principle, be recast into a physicalist paradigm, once viewed from an integral perspective, they substantiate equally well an ontology that posits mind and consciousness as a primal phenomenon.
Application of attentional bias modification to reduce attentional bias and emotional reactivity to stress in mildly depressed individuals
Authors: Baek Soojung , Ha SoSeo , Lee Jang-Han
Published: October 2023

This study aims to verify the effectiveness of attentional bias modification (ABM) in reducing attentional bias related to depression, particularly in the later stages of attention as a pattern of difficulty in disengagement from depression-relevant stimuli, and to assess its effects on emotional reactivity to stress. A total of 78 participants were separated into four groups based on their levels of depression (minimal and mild) and the types of ABM. The positive ABM (pABM) trained participants to disengage their attention from depression-relevant stimuli and directed their attention toward more positive stimuli, whereas the neutral ABM (nABM) was designed to have no effect. The participants underwent a free-viewing task by eye tracker both before and after ABM to observe changes in attentional bias. Subsequently, they reported their emotional response after a stress-inducing task. The group of mildly depressed participants receiving pABM showed significantly less attention to depression-relevant negative affective stimuli and reported significantly decreased negative emotional reactivity to stress compared to the other groups. pABM had an effect on decreasing difficulty in disengaging from depression-relevant negative affective words (DW). However, it did not increase the dwell time on positive affective words (PW) in the current study. This might be due to the short duration of the application of ABM. The current study conducted ABM twice in 1 day, and this might not be enough to increase the dwell time on PA. This study verified that the ABM effectively decreased the attentional bias of depression and its relevant symptom, emotional reactivity to stress.
Treatment-Resistant Depression in America Latina study: one-year follow-up of treatment resistant depression patients under standard of care reveals insights on quality of life, disability, work impairment, and depressive symptoms
Authors: Recco Kelen , Bonetto Gerardo Garcia , Lupo Christian , Nardi Antonio E. , Morales Arnulfo , Becerra-Palars Claudia , Perocco Sergio , Pfau Alanna
Published: October 2023

Introduction

Depressive Disorders are on the rise worldwide. This is also the case in Latin America (LatAm). Treatment-Resistant Depressive Disorder (TRD) poses additional burden to patients with depression. Impacts quality of life (QoL) and other dimensions, and standard of care (SOC) is insufficient to achieve the desired clinical outcomes. Evidence from LatAm is, however, lacking. The present study was devised as a 1-year follow-up of the SOC in TRD patients in LatAm to explore the burden of TRD.

Methods

This was an observational, multinational, longitudinal study. Patients with clinical diagnosis of TRD in LatAm were included in a 1-year follow-up with SOC. Beyond the Sociodemographic characterization, outcome measures were QoL (EQ-5D-5L), disability (Sheehan Disability Scale - SDS), work productivity (Work Productivity and Activity Incapacity Questionnaire: depression - WPAI:D) and depression severity (Patient Health Questionnaire-PHQ9). Patients were assessed every 3-months and comparison was performed based on change from baseline to each visit and end of study (EOS - 12 months).

Results

Patients averaged 48 (± 13.12) years, mostly female (80.9%) and married/consensual union (42.5%) or single patients (34.4%). Despite the SOC treatment, three-quarters of the patients remained symptomatic at EOS, regardless of the significant longitudinal decrease (p ≤ 0.001). Similar trends were found for disability (p ≤ 0.001) -82.2% of the patients reporting work/school disruption at EOS-, percentage of work (34%) and activity impairment (40%) at EOS (p ≤ 0.001) and only 29.2% of patients with depressive severity “none” at EOS (p ≤ 0.001). The results portray the need to improve clinical outcomes in this complex and burdensome disease in LatAm.

Discussion

Here we show that the burden of TRD remains significant in essential dimensions of everyday life at EOS underlining the need for better therapeutic solutions. The improvements in most patients do not provide the desired outcome of return to the state before the condition. Further research should focus on identifying which treatments provide better outcomes in a real-world context.
Prevalence and impact of long COVID-19 among patients with diabetes and cardiovascular diseases in Bangladesh
Authors: Sharif Nadim , Sharif Nazmul , Khan Afsana , Halawani Ibrahim F. , Alzahrani Fuad M. , Alzahrani Khalid J. , Díez Isabel De la Torre , Vargas Debora Libertad Ramírez , Castilla Angel Gabriel Kuc , Parvez Anowar Khasru , Dey Shuvra Kanti
Published: October 2023

Introduction

Co-prevalence of long-COVID-19, cardiovascular diseases and diabetes is one of the major health challenges of the pandemic worldwide. Studies on long-COVID-19 and associated health outcomes are absent in Bangladesh. The main aim of this study was to determine the prevalence and impact of long-COVID-19 on preexisting diabetes and cardiovascular diseases (CVD) on health outcomes among patients in Bangladesh.

Methods

We collected data from 3,250 participants in Bangladesh, retrospectively. Multivariable logistic regression model was used to determine the odds ratio between independent and dependent variables. Kaplan-Meier survival curve was used to determine the cumulative survival.

Results

COVID-19 was detected among 73.4% (2,385 of 3,250) participants. Acute long-COVID-19 was detected among 28.4% (678 of 2,385) and chronic long-COVID-19 among 71.6% (1,707 of 2,385) patients. CVD and diabetes were found among 32%, and 24% patients, respectively. Mortality rate was 18% (585 of 3,250) among the participants. Co-prevalence of CVD, diabetes and COVID-19 was involved in majority of fatality (95%). Fever (97%), dry cough (87%) and loss of taste and smell (85%) were the most prevalent symptoms. Patients with co-prevalence of CVD, diabetes and COVID-19 had higher risk of fatality (OR: 3.65, 95% CI, 2.79–4.24). Co-prevalence of CVD, diabetes and chronic long-COVID-19 were detected among 11.9% patients.

Discussion

Risk of hospitalization and fatality reduced significantly among the vaccinated. This is one of the early studies on long-COVID-19 in Bangladesh.
Computer-aided diagnostic accuracy of pulmonary tuberculosis on chest radiography among lower respiratory tract symptoms patients
Authors: Abuzerr Samer , Zinszer Kate
Published: October 2023

Even though the Gaza Strip is a low pulmonary tuberculosis (TB) burden region, it is well-known that TB is primarily a socioeconomic problem associated with overcrowding, poor hygiene, a lack of fresh water, and limited access to healthcare, which is the typical case in the Gaza Strip. Therefore, this study aimed at assessing the accuracy of the automatic software computer-aided detection for tuberculosis (CAD4TB) in diagnosing pulmonary TB on chest radiography and compare the CAD4TB software reading with the results of geneXpert. Using a census sampling method, the study was conducted in radiology departments in the Gaza Strip hospitals between 1 December 2022 and 31 March 2023. A digital X-ray, printer, and online X-ray system backed by CAD4TBv6 software were used to screen patients with lower respiratory tract symptoms. GeneXpert analysis was performed for all patients having a score > 40. A total of 1,237 patients presenting with lower respiratory tract symptoms participated in this current study. Chest X-ray readings showed that 7.8% (n = 96) were presumptive for TB. The CAD4TBv6 scores showed that 11.8% (n = 146) of recruited patients were presumptive for TB. GeneXpert testing on sputum samples showed that 6.2% (n = 77) of those with a score > 40 on CAD4TB were positive for pulmonary TB. Significant differences were found in chest X-ray readings, CAD4TBv6 scores, and GeneXpert results among sociodemographic and health status variables (P-value < 0.05). The study showed that the incidence rate of TB in the Gaza Strip is 3.5 per 100,000 population in the Gaza strip. The sensitivity of the CAD4TBv6 score and the symptomatic review for tuberculosis with a threshold score of >40 is 80.2%, and the specificity is 94.0%. The positive Likelihood Ratio is 13.3%, Negative Likelihood Ratio is 0.2 with 7.8% prevalence. Positive Predictive Value is 52.7%, Negative Predictive Value is 98.3%, and accuracy is 92.9%. In a resource-limited country with a high burden of neglected disease, combining chest X-ray readings by CAD4TB and symptomatology is extremely valuable for screening a population at risk. CAD4TB is noticeably more efficient than other methods for TB screening and early diagnosis in people who would otherwise go undetected.
Multimodal deep learning for liver cancer applications: a scoping review
Authors: Siam Aisha , Alsaify Abdel Rahman , Mohammad Bushra , Biswas Md. Rafiul , Ali Hazrat , Shah Zubair
Published: October 2023

Background

Hepatocellular carcinoma is a malignant neoplasm of the liver and a leading cause of cancer-related deaths worldwide. The multimodal data combines several modalities, such as medical images, clinical parameters, and electronic health record (EHR) reports, from diverse sources to accomplish the diagnosis of liver cancer. The introduction of deep learning models with multimodal data can enhance the diagnosis and improve physicians' decision-making for cancer patients.

Objective

This scoping review explores the use of multimodal deep learning techniques (i.e., combining medical images and EHR data) in diagnosing and prognosis of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA).

Methodology

A comprehensive literature search was conducted in six databases along with forward and backward references list checking of the included studies. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) extension for scoping review guidelines were followed for the study selection process. The data was extracted and synthesized from the included studies through thematic analysis.

Results

Ten studies were included in this review. These studies utilized multimodal deep learning to predict and diagnose hepatocellular carcinoma (HCC), but no studies examined cholangiocarcinoma (CCA). Four imaging modalities (CT, MRI, WSI, and DSA) and 51 unique EHR records (clinical parameters and biomarkers) were used in these studies. The most frequently used medical imaging modalities were CT scans followed by MRI, whereas the most common EHR parameters used were age, gender, alpha-fetoprotein AFP, albumin, coagulation factors, and bilirubin. Ten unique deep-learning techniques were applied to both EHR modalities and imaging modalities for two main purposes, prediction and diagnosis.

Conclusion

The use of multimodal data and deep learning techniques can help in the diagnosis and prediction of HCC. However, there is a limited number of works and available datasets for liver cancer, thus limiting the overall advancements of AI for liver cancer applications. Hence, more research should be undertaken to explore further the potential of multimodal deep learning in liver cancer applications.
The idea of society: the Spoken World Theory and the ontological conceptualization of society
Authors: Van Langenhove Luk
Published: October 2023

This article presents a new conceptualization of society with the ambition to sharpen thinking about social reality and to better understand how society relates to personhood. This exercise is framed in an attempt to develop the Spoken World Theory, inspired by the thinking of Rom Harré. It involves a radical rethink of the social ontology and is to be seen as an alternative to the traditional conceptualization of society as a social structure that is opposed to individual agency. The proposed alternative is based upon the disentanglement of four aspects of society along the Vygotskian public/private and individual/collective axes. As such, society can be said to manifest itself in four realms: (i) the world as we hear it: a worldwide and history-long ongoing web of conversations; (ii) the world as we see it: a set of materialized social artifacts, including a set of institutional facts; (iii) the world as we imagine it: individual umwelts or worldviews for each person based on appropriated knowledge and moral frameworks; and (iv) the world as we shape it: persons have the power to formulate intentions that they can bring to the conversational space or the space of artifacts. A major consequence of this conceptualization is that it no longer puts society outside human beings, nor that personality is only to be located inside persons. The proposed ontological framework allows us to speak in much clearer terms about how persons and society are entangled with each other in the sense that without the personhood of people, there can be no society, and that without society, people cannot have personhood. Both personhood and society are to be seen as two intertwined mechanisms that allow the individuals of the human species to complement the genetic basis of survival with a system of cultural resources that can be used for coping with everyday life. The article ends with a discussion of the practical implications of social theorizing.
New insights from Norwegian and Swedish sports coaches' employment, practices, and beliefs during the first COVID-19 restriction period
Authors: Severin Anna Cecilia , Skovereng Knut , Björklund Glenn , Hemmestad Liv , Sandbakk Øyvind , Bucher Sandbakk Silvana
Published: October 2023

Introduction

This study (i) examined Norwegian and Swedish sports coaches' employment, practices, and beliefs during the first wave of the COVID-19 pandemic, (ii) compared these aspects between coaches in Norway and Sweden, two countries with clearly different movement restrictions strategies in this period.

Methods

An online survey was distributed to coaches via email and social media. The survey was open between June and August 2020. In total, 348 coaches responded, 141 from Norway, and 207 from Sweden.

Results

Among responders, 2% had lost their job due to the pandemic, 17% had been furloughed, 28% worked from home office, and 39% worked as usual. Norwegian coaches were more likely to work from home (48% vs. 15%, p < .001), while Swedish coaches were more likely to work as usual (60% vs. 9%, p < .001). Coaches in both countries communicated less frequently with their athletes (p < .001) and had less in-person communication (p < .001) compared to pre-Covid levels. Larger declines existed among Norwegian coaches regarding communication frequency (p < .001) and in-person communication (p < .001). Video calls and phone calls usage increased (p < .001 and p = .009 respectively). We recorded low levels of concern among coaches about the effects of the pandemic on their relationship with their athletes. There were considerable levels of concern about athletes’ maintaining their motivation to train (Norway: 43.3%, Sweden: 50.7%), and low levels of concern about the coaches’ relationships with their athletes (Norway: 14.1%, Sweden: 17.8%).

Discussion

Overall, this study showed the imposed movement restrictions had several negative consequences for the employment and work practices of sports coaches in Norway and Sweden. However, it also highlighted that coaches were able to adapt their work practices to the constraints and were able to maintain relationships with their athletes. The consequences raised in this paper can act as a guide during possible future lockdowns.
Análise da influência do sulfato de gentamicina e técnica de resfriamento nas propriedades mecânicas do poli (metacrilato de metila)
Authors: Cardoso Pedro Henrique Novaes , Baraúna Júnior Durval , Fonseca Kaio Luan da Silva , Cordeiro Erlon Rabelo , Idogava Henrique Takashi , Da Silva Alan Christie , Hernandez Luis Iván Negrin , Olivier Nelson Cárdenas
Published: October 2023

O Poli(metacrilato de metila) é um polímero largamente utilizado nas mais diversas aplicações da biomedicina. Na ortopedia, este polímero pode ser utilizado como reforço estrutural em fraturas ósseas, e com isso, garante a integridade física do osso danificado. Com o intuito de evitar a proliferação de micróbios na fratura, uma determinada quantidade de antimicrobiano pode ser adicionada homogeneamente ao Poli(metacrilato de metila). Para prevenir a necrose térmica durante a polimerização, que pode atingir até 100°C, utiliza-se técnicas de resfriamento, garantindo a temperatura ideal de preservação da integridade das células na região da fratura. Este trabalho teve como objetivo avaliar a influência da adição de Sulfato de Gentamicina e aplicação de técnica de resfriamento no comportamento mecânico do Poli(metacrilato de metila) comercializado em três tipos de nomenclaturas comerciais. Para isso, foi utilizada a Microscopia Eletrônica de Varredura, e os ensaios mecânicos de compressão, flexão e torção.  Com estes ensaios, foi possível constatar que o Poli(metacrilato de metila), após ser submetido a técnica de resfriamento e a adição de antimicrobiano, ainda atende os requisitos de resistência mecânica exigidos por normas técnicas que especificam o uso deste material em aplicações ortopédicas, garantindo o uso com segurança para esta aplicabilidade.
Modelos matemáticos originales en conjetura en primos, función de distribución de probabilidades y sistemas de ecuaciones para economía, educación, trabajo, seguridad ciudadana, tecnología y cáncer
Authors: Massa Fernando Gustavo Isa
Published: October 2023

Se presenta un trabajo de investigación en matemáticas de ciencias básicas con tres modelos matemáticos originales, el primero empieza demostrando de diversas maneras la ecuación madre en teoría de sistemas que la ingeniería en sistemas no tenía ecuación madre para culminar con aplicaciones del incremento del sistema de ecuaciones en inversiones, educación y seguridad ciudadana. El segundo modelo es una abstracción en una nueva conjetura en números primos, que invito a la comunidad científica internacional a demostrarla o rechazarla. El tercer modelo es una función de distribución de probabilidades que también puede ser definida como una probabilidad en el intervalo, y cuyas aplicaciones son: números binarios, cáncer e inversiones. Se complementa al tramado matemático original con aplicaciones sensibles y de carácter de urgente solución.
A importância da atividade física no contexto Policial Militar vinculada à construção do centro poliesportivo no 6.º BPM
Authors: Figueredo Anderson Marcelo
Published: October 2023

O presente artigo buscou apresentar uma análise acerca da importância da atividade física no contexto da atividade policial militar, relacionando-a à rotina profissional do policial e aos consequentes prejuízos para sua saúde quando a prática de exercícios físicos não é valorizada. Discutiu-se o impacto negativo da falta dessas atividades na saúde do profissional, bem como as principais doenças e distúrbios dela decorrentes e possíveis soluções. Utilizando o ambiente do 6.º BPM como referência, partiu-se da hipótese de que a construção de um complexo poliesportivo anexo ao terreno do referido Batalhão, além do induzimento às práticas de atividades físicas dentro da Corporação, pode ajudar a melhorar tanto a saúde física quanto a saúde mental dos militares. Utilizou-se a metodologia bibliográfica para levantamento do referencial teórico, bem como o estudo de caso, por meio da aplicação de um questionário, para melhor extrair informações diretamente dos policiais, facilitando assim a oportunidade de relacionar o caso estudado com as bibliografias abordadas. Por fim, houve a conclusão de que parcela das escolas de formação de militares sofre com a falta de instalações próprias para realização de atividades físicas, fazendo com que haja um desinteresse na prática de exercícios por parte desses profissionais, apesar de a maioria deles afirmar que as atividades físicas contribuem para a prevenção de doenças, inclusive as psíquicas. Nesse contexto, um projeto arquitetônico foi apresentado como sugestão para a estrutura do centro poliesportivo anexo ao 6.º BPM.
Presentation of a Patient With Neurobrucellosis: A Case Report in Iran
Authors: Yaghubi Kalurazi Tofigh , Amini-Salehi Ehsan , Hassanipour Soheil , Joukar Farahnaz , Ansar Malek Moien , Soofi Nazila , Jafari Elnaz , Hojati Seyedeh Amineh , Mansour-Ghanaei Fariborz
Published: October 2023

Background: Brucellosis is a common zoonotic infection caused by the bacterial genus Brucella. It is one of the infectious diseases transmissible between humans and animals, and its clinical manifestations are very diverse and misleading. One of these manifestations is central nervous system involvement, which occurs in various forms. Better and more accurate identification of these diverse clinical manifestations can help physicians in the timely diagnosis and treatment of the disease. Case Presentation: In this study, we introduce a sixteen-year-old patient who complained of fever, low back pain, dizziness, and headache for two months. A detailed history of our patient revealed previous contact with sheep and consumption of unpasteurized milk. Further clinical tests confirmed the diagnosis of Brucella meningitis in this patient. Conclusion: Patients with brucellosis can show a wide variety of clinical symptoms, and knowing these different clinical forms can help physicians in the early diagnosis of the disease. In a country like Iran, where brucellosis is endemic, any patient who presents with complex and unexplained neurological complaints, especially those with a history of brucellosis, should be considered for neurobrucellosis.
The Association of NKp46-Positive uNK Cells With a Higher Risk of Recurrent Miscarriage and IVF Failure
Authors: Matouri Maryam , Ghafourian Mehri , Ghadiri Ata , Moramezi Farideh
Published: October 2023

Background: Uterine natural killer (uNK) cells have a significant impact on pregnancy and related complications. Given the importance of receptors in the activity of uNK cells, the present study aimed to determine the number of uNK cells and NKp46 (one of the most important NK cell-activating receptors) expression in the endometrium of women with recurrent miscarriage (RM) or a history of in vitro fertilization (IVF) failure. Materials and Methods: This case-control study was performed on 48 participants, including 16 healthy controls, 27 cases with RM, and 5 cases with repeated implantation failure (RIF) during the mid-luteal phase according to a standardized diagnostic protocol. All participants were assessed using transvaginal ultrasound to determine embryo survival rate and confirm gestational age. Endometrial specimens were collected and subjected to immunohistochemistry (IHC) staining using an anti-human NKp46 antibody expressed by uNK cells. Results: A significantly higher number of cells positive for NKp46 was obtained among two groups of cases versus healthy subjects (patients: 1.46±0.78, controls: 0.82±62, P=0.006), and the number of CD56+cells was significantly higher in patients than in controls (patients: 18.14±7.14, controls: 11.71±6.17, P=0.003). Additionally, there was not a significant difference in the frequency ratio of NKp46+NK cell subset to CD56+uNK cells between the patients (P=0.59) and control healthy group. Conclusion: The increase in the number of uterine NK cells and their cytotoxic activity during implantation and early pregnancy, possibly resulting from an excessive expression of inflammatory cytokines, confirms a significant association between uNK cell activity and a higher risk of RM and RIF. Therefore, immunomodulatory treatments may benefit these patients.