bluuebunny/crossref_metadata_2025 huggingface dataset:
The spectrum of GATA2 deficiency syndrome
Authors: Calvo Katherine R. , Hickstein Dennis D.
Published: December 2022

Inherited or de novo germ line heterozygous mutations in the gene encoding the transcription factor GATA2 lead to its deficiency. This results in a constellation of clinical features including nontuberculous mycobacterial, bacterial, fungal, and human papillomavirus infections, lymphedema, pulmonary alveolar proteinosis, and myelodysplasia. The onset, or even the presence, of disease is highly variable, even in kindreds with the identical mutation in GATA2. The clinical manifestations result from the loss of a multilineage progenitor that gives rise to B lymphocytes, monocytes, natural killer cells, and dendritic cells, leading to cytopenias of these lineages and subsequent infections. The bone marrow failure is typically characterized by hypocellularity. Dysplasia may either be absent or subtle but typically evolves into multilineage dysplasia with prominent dysmegakaryopoiesis, followed in some instances by progression to myeloid malignancies, specifically myelodysplastic syndrome, acute myelogenous leukemia, and chronic myelomonocytic leukemia. The latter 3 malignancies often occur in the setting of monosomy 7, trisomy 8, and acquired mutations in ASXL1 or in STAG2. Importantly, myeloid malignancy may represent the primary presentation of disease without recognition of other syndromic features. Allogeneic hematopoietic stem cell transplantation (HSCT) results in reversal of the phenotype. There remain important unanswered questions in GATA2 deficiency, including the following: (1) Why do some family members remain asymptomatic despite harboring deleterious mutations in GATA2? (2) What are the genetic changes that lead to myeloid progression? (3) What causes the apparent genetic anticipation? (4) What is the role of preemptive HSCT?
Activation priming and cytokine polyfunctionality modulate the enhanced functionality of low-affinity CD19 CAR T cells
Authors: Michelozzi Ilaria M. , Gomez-Castaneda Eduardo , Pohle Ruben V. C. , Cardoso Rodriguez Ferran , Sufi Jahangir , Puigdevall Costa Pau , Subramaniyam Meera , Kirtsios Efstratios , Eddaoudi Ayad , Wu Si Wei , Guvenel Aleks , Fisher Jonathan , Ghorashian Sara , Pule Martin A. , Tape Christopher J. , Castellano Sergi , Amrolia Persis J. , Giustacchini Alice
Published: December 2022

We recently described a low-affinity second-generation CD19 chimeric antigen receptor (CAR) CAT that showed enhanced expansion, cytotoxicity, and antitumor efficacy compared with the high-affinity (FMC63-based) CAR used in tisagenlecleucel, in preclinical models. Furthermore, CAT demonstrated an excellent toxicity profile, enhanced in vivo expansion, and long-term persistence in a phase 1 clinical study. To understand the molecular mechanisms behind these properties of CAT CAR T cells, we performed a systematic in vitro characterization of the transcriptomic (RNA sequencing) and protein (cytometry by time of flight) changes occurring in T cells expressing low-affinity vs high-affinity CD19 CARs following stimulation with CD19-expressing cells. Our results show that CAT CAR T cells exhibit enhanced activation to CD19 stimulation and a distinct transcriptomic and protein profile, with increased activation and cytokine polyfunctionality compared with FMC63 CAR T cells. We demonstrate that the enhanced functionality of low-affinity CAT CAR T cells is a consequence of an antigen-dependent priming induced by residual CD19-expressing B cells present in the manufacture.
Paired bone marrow and peripheral blood samples demonstrate lack of widespread dissemination of some CH clones
Authors: Osman Afaf E. G. , Mencia-Trinchant Nuria , Saygin Caner , Moma Luke , Kim Aelin , Housman Genevieve , Pozsgai Matthew , Sinha Eti , Chandra Pooja , Hassane Duane C. , Sboner Andrea , Sangani Kishan , DiNardi Nick , Johnson Christopher , Wallace Sara S. , Jabri Bana , Luu Hue , Guzman Monica L. , Desai Pinkal , Godley Lucy A.
Published: December 2022

Clonal hematopoiesis (CH) represents clonal expansion of mutated hematopoietic stem cells detectable in the peripheral blood or bone marrow through next generation sequencing. The current prevailing model posits that CH mutations detected in the peripheral blood mirror bone marrow mutations with clones widely disseminated across hematopoietic compartments. We sought to test the hypothesis that all clones are disseminated throughout hematopoietic tissues by comparing CH in hip vs peripheral blood specimens collected at the time of hip replacement surgery. Here, we show that patients with osteoarthritis have a high prevalence of CH, which involve genes encoding epigenetic modifiers and DNA damage repair pathway proteins. Importantly, we illustrate that CH, including clones with variant allele frequencies >10%, can be confined to specific bone marrow spaces and may be eliminated through surgical excision. Future work will define whether clones with somatic mutations in particular genes or clonal fractions of certain sizes are either more likely to be localized or are slower to disseminate into the peripheral blood and other bony sites.
Multiomics links global surfactant dysregulation with airflow obstruction and emphysema in COPD
Authors: Hristova Ventzislava A. , Watson Alastair , Chaerkady Raghothama , Glover Matthew S. , Ackland Jodie , Angerman Bastian , Belfield Graham , Belvisi Maria G. , Burke Hannah , Cellura Doriana , Clark Howard W. , Etal Damla , Freeman Anna , Heinson Ashley I. , Hess Sonja , Hühn Michael , Hall Emily , Mackay Alex , Madsen Jens , McCrae Christopher , Muthas Daniel , Novick Steven , Ostridge Kristoffer , Öberg Lisa , Platt Adam , Postle Anthony D. , Spalluto C. Mirella , Vaarala Outi , Wang Junmin , Staples Karl J. , Wilkinson Tom M.A. ,   on behalf of the MICA II Study group
Published: December 2022

Rationale

Pulmonary surfactant is vital for lung homeostasis as it reduces surface tension to prevent alveolar collapse and provides essential immune-regulatory and antipathogenic functions. Previous studies demonstrated dysregulation of some individual surfactant components in COPD. We investigated relationships between COPD disease measures and dysregulation of surfactant components to gain new insights into potential disease mechanisms.

Methods

Bronchoalveolar lavage proteome and lipidome were characterised in ex-smoking mild/moderate COPD subjects (n=26) and healthy ex-smoking (n=20) and never-smoking (n=16) controls using mass spectrometry. Serum surfactant protein analysis was performed.

Results

Total phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol, surfactant protein (SP)-B, SP-A and SP-D concentrations were lower in COPDversuscontrols (log2fold change (log2FC) −2.0, −2.2, −1.5, −0.5, −0.7 and −0.5 (adjusted p<0.02), respectively) and correlated with lung function. Total phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol, SP-A, SP-B, SP-D, napsin A and CD44 inversely correlated with computed tomography small airways disease measures (expiratory to inspiratory mean lung density) (r= −0.56, r= −0.58, r= −0.45, r= −0.36, r= −0.44, r= −0.37, r= −0.40 and r= −0.39 (adjusted p<0.05)). Total phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol, SP-A, SP-B, SP-D and NAPSA inversely correlated with emphysema (% low-attenuation areas): r= −0.55, r= −0.61, r= −0.48, r= −0.51, r= −0.41, r= −0.31 and r= −0.34, respectively (adjusted p<0.05). Neutrophil elastase, known to degrade SP-A and SP-D, was elevated in COPDversuscontrols (log2FC 0.40, adjusted p=0.0390), and inversely correlated with SP-A and SP-D. Serum SP-D was increased in COPDversushealthy ex-smoking volunteers, and predicted COPD status (area under the curve 0.85).

Conclusions

Using a multiomics approach, we demonstrate, for the first time, global surfactant dysregulation in COPD that was associated with emphysema, giving new insights into potential mechanisms underlying the cause or consequence of disease.
Robust and accurate prediction of self-interacting proteins from protein sequence information by exploiting weighted sparse representation based classifier
Authors: Li Yang , Hu Xue-Gang , You Zhu-Hong , Li Li-Ping , Li Pei-Pei , Wang Yan-Bin , Huang Yu-An
Published: December 2022

Background

Self-interacting proteins (SIPs), two or more copies of the protein that can interact with each other expressed by one gene, play a central role in the regulation of most living cells and cellular functions. Although numerous SIPs data can be provided by using high-throughput experimental techniques, there are still several shortcomings such as in time-consuming, costly, inefficient, and inherently high in false-positive rates, for the experimental identification of SIPs even nowadays. Therefore, it is more and more significant how to develop efficient and accurate automatic approaches as a supplement of experimental methods for assisting and accelerating the study of predicting SIPs from protein sequence information.

Results

In this paper, we present a novel framework, termed GLCM-WSRC (gray level co-occurrence matrix-weighted sparse representation based classification), for predicting SIPs automatically based on protein evolutionary information from protein primary sequences. More specifically, we firstly convert the protein sequence into Position Specific Scoring Matrix (PSSM) containing protein sequence evolutionary information, exploiting the Position Specific Iterated BLAST (PSI-BLAST) tool. Secondly, using an efficient feature extraction approach, i.e., GLCM, we extract abstract salient and invariant feature vectors from the PSSM, and then perform a pre-processing operation, the adaptive synthetic (ADASYN) technique, to balance the SIPs dataset to generate new feature vectors for classification. Finally, we employ an efficient and reliable WSRC model to identify SIPs according to the known information of self-interacting and non-interacting proteins.

Conclusions

Extensive experimental results show that the proposed approach exhibits high prediction performance with 98.10% accuracy on the yeast dataset, and 91.51% accuracy on the human dataset, which further reveals that the proposed model could be a useful tool for large-scale self-interacting protein prediction and other bioinformatics tasks detection in the future.
RLFDDA: a meta-path based graph representation learning model for drug–disease association prediction
Authors: Zhang Meng-Long , Zhao Bo-Wei , Su Xiao-Rui , He Yi-Zhou , Yang Yue , Hu Lun
Published: December 2022

Background

Drug repositioning is a very important task that provides critical information for exploring the potential efficacy of drugs. Yet developing computational models that can effectively predict drug–disease associations (DDAs) is still a challenging task. Previous studies suggest that the accuracy of DDA prediction can be improved by integrating different types of biological features. But how to conduct an effective integration remains a challenging problem for accurately discovering new indications for approved drugs.

Methods

In this paper, we propose a novel meta-path based graph representation learning model, namely RLFDDA, to predict potential DDAs on heterogeneous biological networks. RLFDDA first calculates drug–drug similarities and disease–disease similarities as the intrinsic biological features of drugs and diseases. A heterogeneous network is then constructed by integrating DDAs, disease–protein associations and drug–protein associations. With such a network, RLFDDA adopts a meta-path random walk model to learn the latent representations of drugs and diseases, which are concatenated to construct joint representations of drug–disease associations. As the last step, we employ the random forest classifier to predict potential DDAs with their joint representations.

Results

To demonstrate the effectiveness of RLFDDA, we have conducted a series of experiments on two benchmark datasets by following a ten-fold cross-validation scheme. The results show that RLFDDA yields the best performance in terms of AUC and F1-score when compared with several state-of-the-art DDAs prediction models. We have also conducted a case study on two common diseases, i.e., paclitaxel and lung tumors, and found that 7 out of top-10 diseases and 8 out of top-10 drugs have already been validated for paclitaxel and lung tumors respectively with literature evidence. Hence, the promising performance of RLFDDA may provide a new perspective for novel DDAs discovery over heterogeneous networks.
Genetic diversity and forensic application of Y-filer STRs in four major ethnic groups of Pakistan
Authors: Ikram Muhammad Salman , Mehmood Tahir , Rakha Allah , Akhtar Sareen , Khan Muhammad Imran Mahmood , Al-Qahtani Wedad Saeed , Safhi Fatmah Ahmed , Hadi Sibte , Wang Chuan-Chao , Adnan Atif
Published: December 2022

17 Y-chromosomal STRs which are part of the Yfiler Amplification Kit were investigated in 493 unrelated Pakistani individuals belonging to the Punjabi, Sindhi, Baloch, and Pathan ethnic groups. We have assessed the forensic parameters and population genetic structure for each group. Among the 493 unrelated individuals from four ethnic groups (128 Baloch, 122 Pathan, 108 Punjabi, and 135 Sindhi), 82 haplotypes were observed with haplotype diversity (HD) of 0.9906 in Baloch, 102 haplotypes with HD value of 0.9957 in Pathans, 80 haplotypes with HD value of 0.9924 in Punjabi, and 105 haplotypes with HD value of 0.9945 in the Sindhi population. The overall gene diversity for Baloch, Pathan, Punjabi, and Sindhi populations was 0.6367, 0.6479, 0.6657, and 0.6112, respectively. The results had shown us that Pakistani populations do not have a unique set of genes but share the genetic affinity with regional (Central Asia and Northern India) populations. The observed low gene diversity (heterozygosity) values may be because of endogamy trends and this observation is equally supported by the results of forensic parameters which are mostly static across 4 combinations (minimal STRs, extended 11 Y-STRs, Powerplex 12 Y System, and Yfiler 17 Y-STRs) of STRs in these four populations.
Mutation of gdpS gene induces a viable but non-culturable state in Staphylococcus epidermidis and changes in the global transcriptional profile
Authors: Zhu Tao , Wang Wei , Wang Han , Zhao Yanfeng , Qu Di , Wu Yang
Published: December 2022

Background

In the genome of staphylococci, only the gdpS gene encodes the conserved GGDEF domain, which is the characteristic of diguanylate cyclases. In our previous study, we have demonstrated that the gdpS gene can modulate biofilm formation by positively regulating the expression of ica operon in Staphylococcus epidermidis. Moreover, this regulation seems to be independent of the c-di-GMP signaling pathway and the protein-coding function of this gene. Therefore, the biological function of the gdpS gene remains to be further investigated.

Results

In the present study, it was observed that mutation of the gdpS gene induced S. epidermidis to enter into a presumed viable but nonculturable state (VBNC) after cryopreservation with glycerol. Similarly, when moved from liquid to solid culture medium, the gdpS mutant strain also exhibited a VBNC state. Compared with the wild-type strain, the gdpS mutant strain autolyzed more quickly during storage at 4℃, indicating its increased susceptibility to low temperature. Transcriptional profiling analysis showed that the gdpS mutation affected the transcription of 188 genes (92 genes were upregulated and 96 genes were downregulated). Specifically, genes responsible for glycerol metabolism were most markedly upregulated and most of the altered genes in the mutant strain are those involved in nitrogen metabolism. In addition, the most significantly downregulated genes included the betB gene, whose product catalyzes the synthesis of glycine betaine and confers tolerance to cold.

Conclusion

The preliminary results suggest that the gdpS gene may participate in VBNC formation of S. epidermidis in face of adverse environmental factors, which is probably achieved by regulating expression of energy metabolism genes. Besides, the gdpS gene is critical for S. epidermidis to survive low temperature, and the underlying mechanism may be partly explained by its influence on expression of betB gene.
De novo transcriptome sequencing of Impatiens uliginosa and the analysis of candidate genes related to spur development
Authors: Li Yang , Wei Chun-Mei , Li Xin-Yi , Meng Dan-Chen , Gu Zhi-Jia , Qu Su-Ping , Huang Mei-Juan , Huang Hai-Quan
Published: December 2022

Background

Spur, a structure capable of producing and storing nectar, not only plays a vital role in the pollination process but also promotes the rapid diversification of some plant lineages, which is considered a key innovation in plants. Spur is the focus of many studies, such as evolution and ecological hypothesis, but the current understanding of spur development is limited. High-throughput sequencing of Impatiens uliginosa was carried out to study the molecular mechanism of its spur development, which is believed to provide some insights into the spur development of Impatiens.

Results

Transcriptomic sequencing and analysis were performed on spurs and limbs of I. uliginosa at three developmental stages. A total of 47.83 Gb of clean data were obtained, and 49,716 unigene genes were assembled. After comparison with NR, Swiss-Prot, Pfam, COG, GO and KEGG databases, a total of 27,686 genes were annotated successfully. Through comparative analysis, 19,356 differentially expressed genes were found and enriched into 208 GO terms and 146 KEGG pathways, among which plant hormone signal transduction was the most significantly enriched pathway. One thousand thirty-two transcription factors were identified, which belonged to 33 TF families such as MYB, bHLH and TCP. Twenty candidate genes that may be involved in spur development were screened and verified by qPCR, such as SBP, IAA and ABP.

Conclusions

Transcriptome data of different developmental stages of spurs were obtained, and a series of candidate genes related to spur development were identified. The importance of genes related to cell cycle, cell division, cell elongation and hormones in spur development was clarified. This study provided valuable information and resources for understanding the molecular mechanism of spur development in Impatiens.
Gastrodin improves neuroinflammation-induced cognitive dysfunction in rats by regulating NLRP3 inflammasome
Authors: Zheng Xue , Gong Taowu , Tang Chunchun , Zhong Yuanping , Shi Lu , Fang Xu , Chen Dongqin , Zhu Zhaoqiong
Published: December 2022

Neuroinflammation is the main pathological mechanism of cognitive dysfunction caused by neurodegenerative diseases, and effective preventive and therapeutic measures are not available. We predicted the key targets of gastrodin’s effects upon neuroinflammation through Network Pharmacology and molecular docking. Then the predicted targets were used to study how gastrodin affected cognitive dysfunction triggered by lipopolysaccharide-induced neuroinflammation in rats and its mechanisms. Three-month-old male rats were intraperitoneally injected with lipopolysaccharide for 3 days (d), 7 d and 14 d respectively. Gastrodin improved learning and memory ability of rats with neuroinflammation. Lipopolysaccharide enhanced the levels of pro-inflammatory cytokines, such as TNF-α, IL-1β and IL-6, in rat hippocampus, which could be reversed by gastrodin. Gastrodin also inhibited the activation of microglia. Our findings suggested that gastrodin exerted neuroprotective effects in rats with neuroinflammation by impacting the TLR4-NF-kB-NLRP3 pathway. Therefore, gastrodin may be a potential therapeutic agent for neuroinflammation-induced cognitive dysfunction.
Case study research and causal inference
Authors: Green Judith , Hanckel Benjamin , Petticrew Mark , Paparini Sara , Shaw Sara
Published: December 2022

Case study methodology is widely used in health research, but has had a marginal role in evaluative studies, given it is often assumed that case studies offer little for making causal inferences. We undertook a narrative review of examples of case study research from public health and health services evaluations, with a focus on interventions addressing health inequalities. We identified five types of contribution these case studies made to evidence for causal relationships. These contributions relate to: (1) evidence about system actors’ own theories of causality; (2) demonstrative examples of causal relationships; (3) evidence about causal mechanisms; (4) evidence about the conditions under which causal mechanisms operate; and (5) inference about causality in complex systems. Case studies can and do contribute to understanding causal relationships. More transparency in the reporting of case studies would enhance their discoverability, and aid the development of a robust and pluralistic evidence base for public health and health services interventions. To strengthen the contribution that case studies make to that evidence base, researchers could: draw on wider methods from the political and social sciences, in particular on methods for robust analysis; carefully consider what population their case is a case ‘of’; and explicate the rationale used for making causal inferences.
How stressful was the COVID-19 pandemic for residents specializing in family practice?. A study of stressors and psychological well-being of physicians in further training specializing in family practice (GP trainees) within a pandemic context
Authors: von Oltersdorff-Kalettka Anna-Maria , Meinel Janina , Voigt Karen , Mundt Thomas , Bleckwenn Markus , Bergmann Antje , Gottschall Mandy
Published: December 2022

Background

The coronavirus pandemic poses many challenges for medical personnel. During the first phase of the pandemic, psychological stress became increasingly apparent. This was a complex and difficult situation, especially for physician residents specializing in family practice (GP trainees), who were not yet able to draw on years of practical experience. In this context, the Kompetenzzentrum Weiterbildung Allgemeinmedizin Sachsen (Competence Center for Continuing Education in General Medicine Saxony) (KWASa) developed a survey on how to deal with the concerns and challenges perceived at the time. The purpose of the study was to obtain information on psychological well-being in the pandemic context, as well as on expectations, fears, and protective measures in everyday work. The aim was to identify stress factors for general practice (GP) trainees during a pandemic situation to be able to consider the support needs in the design of future residency training programs, especially for GP trainees.

Methods

An online questionnaire was distributed from May 5, 2020 to June 4, 2020 among GP trainees enrolled in KWASa since 2018. The questionnaire consisted of standardized items, which were evaluated descriptively, and open-ended items with free-text answers, which were evaluated according to the principle of qualitative content analysis.

Results

The results show the relevance of the topic as 61% of respondents indicated that they were concerned about the coronavirus. Most GP trainees also gave an affirmative response regarding emotional challenges. In this context, various stressors could be identified within both the professional and personal environments. There were four particularly salient factors: (1) the fear of infecting one’s family as well as patients with the SARS-CoV-2 virus; (2) missing or insufficiently existing protective measures; (3) an increased need for consultation due to unpredictable patient behavior as well as uncertainties in patient treatment; and (4) communication difficulties within the collegial environment.

Conclusions

The study aimed to identify the support needs of GP trainees in crisis situations such as the COVID-19 pandemic. The results of the survey can be used for the development of suitable continuing education programs for physicians in further training.
The postoperative prognosis of older intertrochanteric fracture patients as evaluated by the Chang reduction quality criteria
Authors: He Miao , Liu Jian , Deng Xu , Zhang Xiaoxing
Published: December 2022

Objective

The aim of this study was to investigate the relationship between the Chang reduction quality criteria (CRQC) and the outcome of intertrochanteric fractures in older adults according to follow-up time.

Methods

This was a retrospective analysis of 389 older adult patients with intertrochanteric fractures treated surgically from January 2019 to June 2021, including 130 males and 259 females aged 84.6 (77.5–89.7) years. Patient survival was determined by telephone as the time between admission to hospital for fracture and death or until the study deadline (June 1, 2022). According to the CRQC, the patients were divided into the Poor, Acceptable, and Excellent groups. Univariate and multivariate Cox proportional hazard models were used to assess the association between CRQC and all-cause mortality in older adult intertrochanteric fractures at 1 year and the total follow-up time. Further subgroup analysis was performed according to different clinical and biological characteristics to improve the accuracy of the results.

Results

The mortality rates were 24.7% and 15.4% at 1 year and the total follow-up time, respectively. Both at one year and the total follow-up time, the mortality of the CRQC-Excellent group was significantly lower than that of the CRQC-Acceptable group (p.adj < 0.05) and the CRQC-Poor group (p.adj < 0.05). After multifactor adjustment, CRQC grades of Acceptable and Poor were independent risk factors affecting the overall and 1-year mortality. In addition, advanced age, ≥ 1 comorbidities, ASA 3 + 4, and prolonged preoperative waiting time were independent risk factors for survival at the total follow-up time. At 1 year, only ASA 3 + 4 and prolonged preoperative waiting time were independent risk factors for survival. Subgroup analysis according to different characteristics at the total follow-up time and at one year showed that in most subgroups, a decrease in the CRQC grade was significantly associated with an increase in all-cause mortality (p for trend < 0.05).

Conclusions

This study highlights that CRQC grades of Acceptable and Poor are associated with increased all-cause mortality in older adult intertrochanteric fractures. We should attempt to achieve good reduction of these fractures.
Determinants of post-stroke depression among stroke survivors at University of Gondar Hospital, Northwest Ethiopia: a case-control study
Authors: Fantu Ephrem , Hailu Workagegnehu , Bekele Nebiyu , Tsegaye Tewodros , Tadesse Melaku , Asres Mezgebu Silamsaw
Published: December 2022

Background

Stroke is one of the most common causes of disability among adults. Post-stroke depression (PSD) is a frequent neuropsychiatric complication in stroke patients. Despite the increasing prevalence of stroke, there is a paucity of data on PSD and its determinants among stroke survivors in developing countries like Ethiopia. We aim to assess the factors associated with PSD in survivors of stroke.

Method

A hospital-based unmatched case-control study was conducted during the period of February to July 2020 at University of Gondar Hospital among stroke survivors. Study subjects were recruited consecutively. Socio-demographic and clinical data were obtained from patients’ interviews and medical record reviews. A diagnosis of PSD was made using the Patient Health Questionnaire (PHQ-9). EpiData version 3.1 was used to enter data, and SPSS version 26 was used to analyze it. Bivariate and multivariate logistic regressions were fitted to identify associated variables. The adjusted odds ratio (AOR) with 95% confidence interval (CI) and p-value 0.05 were used to determine the significance of the association.

Result

A total of 240 stroke survivors were included in the study (80 cases and 160 controls). The mean age was 60.8 years (SD ± 14.3) with an equal sex distribution. Variables statistically associated with PSD were male gender (AOR = 3.5, 95% CI: 1.64-7.46 C, P-value = 0.001), subcortical location of the largest lesion (AOR = 2.42, 95% CI: 1.06–5.56, p-value = 0.036), severity of the stroke (AOR = 52.34, 95% CI:10.64-256.87, p-value = 0.000), physical disability (AOR = 5.85. 95% CI:1.94–17.65, p-value = 0.002), previous history of stroke or transient ischemic attack (AOR = 5.90, 95% CI:2.04–17.10, p-value = 0.001) and ischemic heart disease (AOR = 9.97, 95% CI:3.4-29.22, p-value = 0.000).

Conclusion

Important factors in the occurrence of PSD in this study include prior history of stroke, physical disability, severity of the stroke, subcortical location of the lesion, male gender, and ischemic heart disease. Stroke patients with such factors need routine screening for PSD, particularly in LMICs where there is uncoordinated post-stroke care, a shortage of neurologists and mental health practitioners.
A case of discrepancy between three ERA tests in a woman with repeated implantation failure complicated by chronic endometritis
Authors: Ota Kuniaki , Takahashi Toshifumi , Mitsui Junichiro , Kuroda Kishio , Hiraoka Kenichiro , Kawai Kiyotaka
Published: December 2022

Background

Endometrial receptivity array (ERA) is used to determine the timing of embryo transfer (ET) synchronized with the window of implantation (WOI). The effectiveness and evaluation of ERAs in women with recurrent implantation failure remain controversial. We report the case of a patient with recurrent implantation failure that raises the issue of reproducibility of ERA tests.

Case report

A 36-year-old Japanese woman with secondary infertility who had previously given birth failed to conceive after three frozen-thawed embryo transfer (FET) cycles. An ERA test was conducted to confirm the WOI. The first ERA test was performed 125 h after progesterone exposure. The laboratory reported that the endometrium was in a non-receptive (post-receptive) phase, and recommended retesting 101 h after progesterone exposure. A simultaneous chronic endometritis (CE) test showed a score of 3. After the antibiotics administration to treat CE, the second ERA test was performed after 101 h of progesterone exposure. The laboratory reported that the endometrium had not reached the WOI and estimated the WOI to be 113 ± 3 h after progesterone exposure. The third ERA test was performed 113 h after progesterone exposure. The laboratory reported that the endometrium was in a non-receptive (pre-receptive) phase and estimated the WOI to be 137 ± 3 h after progesterone exposure. A CE test performed at the same time as the second and third ERA tests showed a score of 1 for the collected endometrium. According to the third ERA test results, the vitrified-warmed blastocyst was transferred at 137 h of progesterone exposure. Pregnancy was achieved and the patient had an uncomplicated vaginal delivery at 39 weeks. One year later, another pregnancy was achieved after FET at 137 h of progesterone exposure, and the patient delivered at 33 weeks due to an unexpected membrane rupture.

Conclusion

Because the results of the ERA test may vary in the presence of CE, CE should be diagnosed simultaneously with or before conducting ERA tests. If CE is diagnosed, ERA testing should be performed after treatment with antimicrobials or other drugs.
Analysis of risk factors of early intraventricular hemorrhage in very-low-birth-weight premature infants: a single center retrospective study
Authors: Zhao Ying , Zhang Wanxian , Tian Xiuying
Published: December 2022

Background

This study aimed to determine the risk factors of early intraventricular hemorrhage (IVH) in very-low-birth-weight (VLBW) premature infants in China to guide early interventions and improve the survival and quality of life of these infants.

Methods

Data on 421 VLBW premature infants admitted to the neonatal intensive care unit of Tianjin Central Hospital of Gynecology Obstetrics between July 2017 and July 2019 were retrospectively evaluated. Data on head ultrasound results, maternal pregnancy complications, and perinatal conditions were reviewed to evaluate the association between maternal and neonatal factors and the development and severity of IVH.

Results

Univariate analysis showed that the incidence of early IVH was significantly higher in neonates with early gestational age, delivered after spontaneous labor, low birth weight, 5-minute Apgar score ≤ 7, invasive mechanical ventilation, and early onset sepsis (χ2 = 11.087, 16.868, 4.779, 11.170, 6.655, and 6.260, respectively;P < 0.05), but it was significantly lower in the presence of gestational hypertension (χ2 = 4.373,P = 0.037). In addition, severe IVH was significantly associated with early gestational age, low birth weight, 5-minute Apgar score ≤ 7, and neonatal sepsis (χ2 = 11.599, 8.263, 11.172, and 7.749, respectively;P < 0.05). Logistic regression analysis showed that antenatal glucocorticoid use was associated with significantly reduced incidence of severe IVH (OR = 0.095, 95% CI = 0.012–0.739,P = 0.024).

Conclusion

Appropriate mode of delivery may effectively reduce the incidence of IVH in VLBW premature infants. The antenatal glucocorticoid use may also protect against severe IVH. The focus on steroid prophylaxis, mode of delivery and prevention of perinatal asphyxia should be stressed in China.
DEM-TACE as the initial treatment could improve the clinical efficacy of the hepatocellular carcinoma with portal vein tumor thrombus: a retrospective controlled study
Authors: Chen Junwei , Lai Lisha , Luo Junyang , Wang Haofan , Li Mingan , Huang Mingsheng
Published: December 2022

Background

Conventional-transarterial chemoembolization (C-TACE) was proven to improve overall survival (OS) in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT), drug-eluting microsphere-TACE (DEM-TACE) was supposed to provide more benefit than C-TACE in this respect.

Purpose

To compare the safety and efficacy between DEM-TACE and C-TACE as the initial treatment in HCC patients with PVTT and to identify prognostic factors of OS.

Methods

The medical records of advanced HCC patients with PVTT who underwent DEM-TACE or C-TACE as the initial thearpy from September 2015 with mean follow-up time 14.9 ± 1.2 (95% CI 12.6–17.2) months were retrospectively evaluated. A total of 97 patients were included, 49 patients in the DEM-TACE group and 48 in the C-TACE group. Adverse events (AEs) related to TACE were compared. Tumor and PVTT radiologic response, time to tumor progression (TTP) and OS were calculated and compared in both groups.

Results

Patients in DEM-TACE group had a better radiologic response (Tumr response: 89.8% vs. 75.0%; PVTT response: 85.7% vs. 70.8%; overall response: 79.6% vs. 58.3%, P = 0.024) and longer TTP (7.0 months vs. 4.0 months, P = 0.040) than patients in C-TACE group. A lower incidence of abdominal pain was found in the DEM-TACE group than in C-TACE group (21 vs. 31, P = 0.032), but there were no significant differences between DEM-TACE and C-TACE patients in any other AEs reported. When compared to C-TACE, DEM-TACE also showed significant OS benefits (12.0 months vs. 9.0 months, P = 0.027). DEM-TACE treatment, the absence of arterioportal shunt (APS), lower AFP value and better PVTT radiologic response were the independent prognostic factors for OS in univariate/multivariate analyses, which provided us with a guide for better patient selection.

Conclusions

Based on our retrospective study, DEM-TACE can be performed safely and might be superior to C-TACE as the initial treatment for HCC patients with PVTT.

Trial registration

Retrospectively registered.
Improving community coverage of Japanese encephalitis vaccination: lessons learned from a mass campaign in Battambang Province, Cambodia
Authors: Thigpen Michael C. , Sarath Svay , Soeung Sann Chan , Vichit Ork , Kitsutani Paul , Sandhu Hardeep , Gregory Christopher , Fischer Marc , Morn Chheng , Hills Susan L.
Published: December 2022

A mass Japanese encephalitis (JE) immunization campaign for children aged 9 months through 12 years was conducted in 2013 in Battambang province, western Cambodia. Vaccinators working at almost 2,000 immunization posts in approximately 800 villages provided vaccinations to almost 310,000 children using one dose of Chengdu Institute of Biological Products’ live, attenuated SA14-14-2 JE vaccine (CD-JEV), achieving a coverage rate of greater than 90%. Lessons learned, in general for mass vaccination campaigns and specifically for vaccination with CD-JEV, are described. These observations will be of benefit for public health officials and to help inform planning for future campaigns for JE or other vaccine-preventable diseases in Cambodia and elsewhere.
HIV care experiences and health priorities during the first wave of COVID-19: clients’ perspectives – a qualitative study in Lusaka, Zambia
Authors: Mukamba Njekwa , Sharma Anjali , Mwamba Chanda , Nyirenda Herbert , Foloko Marksman , Lumbo Kasapo , Christopoulos Katerina , Simbeza Sandra , Sikombe Kombatende , Holmes Charles B. , Geng Elvin H. , Sikazwe Izukanji , Bolton-Moore Carolyn , Beres Laura K.
Published: December 2022

Background

The novel COVID-19 pandemic threatened to disrupt access to human immunodeficiency (HIV) treatment for persons living with HIV (PLHIV), two-thirds of whom live in sub-Saharan Africa. To inform a health system response supportive of continuity of care, we sought to understand clients’ HIV care experiences and health priorities during the first wave of COVID-19 outbreak in Lusaka, Zambia.

Methods

Leveraging a study cohort of those who completed periodic SMS surveys on HIV care, we purposefully sampled 25 PLHIV after first confirmed COVID-19 case was reported in Zambia on 18thMarch 2020. We phone-interviewed participants, iteratively refining interview guide to capture emergent themes on COVID-19 awareness, health facility interactions, and social circumstances, which we analyzed using matrix analysis.

Results

All participants were aware of COVID-19, and HIV care experiences and health priorities of clients were affected by associated changes at health system, household, and individual level. The health system instituted early clinic visits to provide 6-months of antiretroviral therapy (ART) for stable patients and 3-months for unstable patients to reduce clinic visits and wait times. Most patients welcomed this long-desired extended appointment spacing. Some reported feeling respected and engaged when health care workers telephoned requesting their early clinic visit. However, others felt discouraged by an absence of physical distancing during their clinic visit due to ‘severe acute respiratory syndrome coronavirus 2’ (SARS-CoV-2) infection concerns. Several expressed a lack of clarity regarding next viral load monitoring date and means for receiving results. Patients suggested regular patient-facility communication by telephone and SMS. Patients emphasized that COVID-19 restrictions led to loss of employment and household income, exacerbating poverty and difficulties in taking ART. At individual level, most participants felt motivated to stay healthy during COVID-19 by ART adherence and regular laboratory monitoring.

Conclusions

Clients’ HIV care and health priorities during the first wave of COVID-19 in Lusaka province were varied with a combination of positive and negative experiences that occurred especially at health system and individual levels, while at household level, the experiences were all negative. More research is needed to understand how patients practice resiliency in the widespread context of socio-economic instability. Governments and patients must work together to find local, health systems solutions to support ART adherence and monitoring. Additionally, the health system should consider how to build on changes for long-term HIV management and service delivery.
Sexual harassment among employees and students at a large Swedish university: who are exposed, to what, by whom and where – a cross-sectional prevalence study
Authors: Agardh A. , Priebe G. , Emmelin M. , Palmieri J. , Andersson U. , Östergren P-O
Published: December 2022

Background

Sexual harassment (SH) in the workplace is prevalent and associated with poor health. Universities are large workplaces with complex formal and informal power relations, which may influence the prevalence of SH. Although employees and students share the university context, few studies on SH have included both groups. The overall aim of the study was to investigate SH among employees and students at a large Swedish public university regarding types of harassment, prevalence in different groups, characteristics of the perpetrators, and the circumstances in which it occurs.

Methods

A cross-sectional analysis was performed, based on a web-based survey with 120 items that was sent out to all staff, including PhD students (N = 8,238) and students (N = 30,244) in November 2019. The response rate was 33% for staff and 32% for students. Exposure to SH was defined as having experienced at least one of ten defined SH behaviors during their work or studies.

Results

Among women, 24.5% of staff and 26.8% of students reported having been exposed to SH. The corresponding figures were 7.0% and 11.3% for male staff and students and 33.3% and 29.4% for non-binary individuals among staff and students. Unwelcome comments, suggestive looks or gestures, and ‘inadvertent’ brushing or touching were the three most common forms of reported harassment, both among staff and students. Attempted or completed rape had been experienced by 2.1% of female and 0.6% of male students. Male and female perpetrators were reported by about 80% and 15%, respectively, of exposed participants. Among staff most reported events occurred during the everyday operation of the university, while among students the majority of the events took place during social events linked to student life. When exposed to a perpetrator from the same group (staff or students), women reported more often being in a subordinate power position in relation to the perpetrator.

Conclusions

The results indicate that sexual harassment is common in the university context, and interventions and case management routines of events should consider power relations between victim and perpetrator, as well as the various contexts within which sexual harassment takes place.
Symptoms of depression and anxiety, and unmet healthcare needs in adults during the COVID-19 pandemic: a cross-sectional study from the Canadian Longitudinal Study on Aging
Authors: Khattar Jayati , Griffith Lauren E. , Jones Aaron , De Rubeis Vanessa , de Groh Margaret , Jiang Ying , Basta Nicole E. , Kirkland Susan , Wolfson Christina , Raina Parminder , Anderson Laura N. ,   the Canadian Longitudinal Study on Aging (CLSA) Team, Costa Andrew , Balion Cynthia , Asada Yukiko , Cossette Benoȋt , Levasseur Melanie , Hofer Scott , Paterson Theone , Hogan David , McMillan Jacqueline , Liu-Ambrose Teresa , Menec Verena , St. John Philip , Mugford Gerald , Gao Zhiwei , Taler Vanessa , Davidson Patrick , Wister Andrew , Cosco Theodore
Published: December 2022

Background

The COVID-19 pandemic disrupted access to healthcare services in Canada. Research prior to the pandemic has found that depression and anxiety symptoms were associated with increased unmet healthcare needs. The primary objective of this study was to examine if mental health was associated with perceived access to healthcare during the pandemic

Methods

A cross-sectional study was conducted using data from 23,972 participants (aged 50-96) in the Canadian Longitudinal Study on Aging COVID-19 Exit Survey (Sept-Dec 2020). We used logistic regression to estimate how the presence of depression and anxiety symptoms, defined using scores of ≥10 on the Center for Epidemiologic Studies Depression Scale and ≥10 on the Generalized Anxiety Disorder Scale, were associated with the odds of reporting: 1) challenges accessing healthcare, 2) not going to a hospital or seeing a doctor when needed, 3) experiencing barriers to COVID-19 testing. Models were adjusted for sex, age, region, urban/rural residence, racial background, immigrant status, income, marital status, work status, chronic conditions, and pre-pandemic unmet needs.

Results

The presence of depressive (aOR=1.96; 95% CI=1.82, 2.11) and anxiety symptoms (aOR=2.33; 95% CI=2.04, 2.66) compared to the absence of these symptoms were independently associated with higher odds of challenges accessing healthcare. A statistically significant interaction with sex suggested stronger associations in females with anxiety. Symptoms of depression (aOR=2.88; 95% CI=2.58, 3.21) and anxiety (aOR=3.05; 95% CI=2.58, 3.60) were also associated with increased odds of not going to a hospital or seeing a doctor when needed. Lastly, depressive (aOR=1.99; 95% CI=1.71, 2.31) and anxiety symptoms (aOR=2.01; 95% CI=1.58, 2.56) were associated with higher odds of reporting barriers to COVID-19 testing. There was no significantly significant interaction with sex for the latter two outcomes.

Conclusion

The presence of depression and anxiety symptoms were strongly associated with perceived unmet healthcare needs during the COVID-19 pandemic. Interventions to improve healthcare access for adults with depression and anxiety during the pandemic may be necessary.
Effectiveness of an online education program for asthma patients in general practice: study protocol for a cluster randomized controlled trial
Authors: Eck Stefanie , Hapfelmeier Alexander , Linde Klaus , Schultz Konrad , Gensichen Jochen , Sanftenberg Linda , Kühlein Thomas , Stark Stefanie , Gágyor Ildikó , Kretzschmann Christian , Schneider Antonius ,   for the Bavarian Practice-Based Research Network (BayFoNet)
Published: December 2022

Background

Asthma education programs (AEPs) have been shown to increase quality of life and reduce emergency treatments and hospital admissions. Despite the proven benefits, only a minority of asthma patients attend such programs. To increase the number of educated patients, an online education program (electronic AEP, eAEP) for asthma patients has been developed. The present study aims to investigate the effectiveness of the eAEP in terms of asthma knowledge, asthma control and emergency treatments in general practice settings.

Methods

This is a cluster randomized controlled trial including 100 patients with bronchial asthma from 20 general practices in Bavaria, Germany. General practices will be randomly assigned to either the intervention or control group. Patients in the intervention group will receive access to the eAEP and instructions to complete this program within two weeks. Patients in the control group will receive usual care including a referral to face-to-face AEP (fAEP) by a certified primary care physician or a pulmonologist according to guideline recommendations. Furthermore, patients of both the intervention and control groups will be invited to a follow-up consultation in their general practice after completion of the eAEP and fAEP (three weeks and twelve weeks after study inclusion, respectively) to discuss any open issues. Outcomes for both groups will be assessed at baseline (t0), after two weeks (t1), three months (t2) and six months (t3). The primary outcome is the comparison of asthma knowledge gain between intervention and control groups after completion of the eAEP (two weeks after study inclusion) and fAEP (twelve weeks after study inclusion), respectively. Secondary outcomes include asthma control, frequency of emergency treatments, patient autonomy as well as attitudes towards asthma medication.

Discussion

The results of the present trial will provide knowledge about the effectiveness of an online education program for asthma patients compared to usual care in primary care.

Trial registration

German Clinical Trials Register (DRKS), DRKS00028805. Registered 22 April 2022.