bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-Term Outcomes of Ascending Sliding Arch Aortoplasty
Authors: Yoneyama Fumiya , Kalustian Alyssa B. , McKenzie E. Dean , Heinle Jeffrey S. , Doan Tam T. , Binsalamah Ziyad
Published: March 2024

Background: Coarctation of the aorta can be associated with significant hypoplasia of the aortic arch. In contrast to patch aortoplasty, ascending sliding arch aortoplasty uses viable autologous tissue for potential growth in children. We reviewed the mid- to long-term outcomes of this technique. Methods: Between 2002 and 2023, 28 patients underwent ascending sliding arch aortoplasty for the patients with coarctation of the aorta (n = 22) and interrupted aortic arch (n = 2). Four patients underwent previous surgical coarctation repair at other institutions. The median patient age and body weight were 28.5 months (3 weeks to 15.6 years) and 13.4 kg (3.7-70 kg), respectively. Results: Although one patient had a recurrent nerve injury postoperatively, there were no other major morbidities or mortalities. The last follow-up echocardiography demonstrated that the mean peak velocity improved from 3.9 ± 0.6 to 0.9 ± 0.8 m/s, and the pressure gradient improved from 63.6 ± 21.5 to 7.1 ± 7.7 mm Hg. The postoperative diameters of the ascending aorta, proximal arch, distal arch, and isthmus all increased significantly. The mean postoperative length of stay was 5.9 ± 2.1 days, and the median follow-up time was 7.3 years (10 days to 20.5 years). No reoperation or catheterization-based intervention was performed for residual coarctation. Conclusions: Ascending sliding arch aortoplasty is safe and effective for treating coarctation of the aorta with aortic arch hypoplasia. This technique is applicable for children ranging in size from neonates to older children (or adolescents), recurrent coarctation cases, and provides complete relief of narrowing by utilizing viable native aortic tissue.
Reporting a Cyber Security Breach: How Organizations Respond
Authors: Naidoo Jef , Dulek Ron , Butler Seth , Baily Brooke
Published: March 2024

Cyber breaches and ransomware attacks now occur so frequently that they have become facets of organizational life. These breaches are unique in that they are initially silent; a limited number of organizational members know about the incident so firms usually have ample time to prepare a Cyber Breach Revelation (CBR). This study analyzes 378 press releases acknowledging a cyber security breach. It finds four response clusters that highlight how compromised organizations reveal cyberattacks to external stakeholders: (1) empathetic acknowledgment; (2) assurance of the organization’s breach-handling capability; (3) restoration of confidence; and, (4) re-establishment of trust and loyalty. These clusters provide meaningful insights as to how firms reveal cyber breaches to their stakeholders and, equally as important, open the door for further studies as to the effectiveness and sequencing of these approaches.
Intravenous alteplase in minor nondisabling ischemic stroke: A systematic review and meta-analysis
Authors: Alhazzani Adel , Al-Ajlan Fahad S , Alkhiri Ahmed , Almaghrabi Ahmed A , Alamri Aser F , Alghamdi Basil A , Salamatullah Hassan K , Alharbi Abdullah R , Almutairi Maher B , Chen Hui-Sheng , Wang Yongjun , Abdalkader Mohamad , Turc Guillaume , Khatri Pooja , Nguyen Thanh N
Published: March 2024

Background:

Minor ischemic stroke, defined as National Institute of Health Stroke Scale score of 0–5 on admission, represents half of all acute ischemic strokes. The role of intravenous alteplase (IVA) among patients with minor stroke is inconclusive; therefore, we evaluated clinical outcomes of these patients treated with or without IVA.

Materials and methods:

We searched Medline, Embase, Scopus, and the Cochrane library until August 1, 2023. Inclusion was restricted to the English literature of studies that reported on minor nondisabling stroke patients treated with or without IVA. Odds ratios (ORs) with their corresponding 95% CIs were utilized using a random-effects model. Efficacy outcomes included rates of excellent (modified Rankin scale [mRS] of 0–1) and good (mRS of 0–2) functional outcome at 90 days. The main safety outcome was symptomatic intracerebral hemorrhage (sICH).

Results:

Five eligible studies, two RCTs and three observational studies, comprising 2764 patients (31.8% female) met inclusion criteria. IVA was administered to 1559 (56.4%) patients. Pooled analysis of the two RCTs revealed no difference between the two groups in terms of 90-days excellent functional outcomes (OR 0.76 [95% CI, 0.51–1.13]; I2 = 0%) and sICH rates (OR 3.76 [95% CI, 0.61–23.20]). No significant differences were observed between the groups in terms of good functional outcomes, 90-day mortality, and 90-day stroke recurrence.

Conclusion:

This meta-analysis of minor nondisabling stroke suggests that IVA did not prove more beneficial compared to no-IVA.
Intragastric injection of botulinum toxin in the treatment of obesity: a single-center study
Authors: Köseoğlu Hasan Tankut , Kenarli Kerem , Akbay Ahmet , Erdoğan Çağdaṣ , Macif Alper , Göktaṣ Meryem Didem , Hamamci Mevlüt , Kalkan Çağdaṣ , Sarialtin Firathan , Yüksel Mahmut
Published: March 2024

Background:

In recent years, various novel surgical and non-surgical therapeutic options have been developed for treating obesity. Due to its disputed success, intragastric botulinum toxin A (BTX-A) injection is still being debated.

Objectives:

We aim to contribute to this controversial issue in the literature by sharing our center’s findings regarding intragastric BTX-A injections in the treatment of obesity.

Design:

Patients with a body mass index (BMI) of greater than 25 kg/m2 and at least one obesity-related complication, or a BMI of greater than 30 kg/m2 without complications, were eligible for the study if they were between the ages of 18 and 65.

Methods:

Following the same procedure, two endoscopists administered BTX-A to all patients. All patients were evaluated for obesity by measuring their lipid profile, hormone profile, and insulin resistance level before treatment.

Results:

In our study on 82 patients, we saw a significant mean weight loss (−9.2 kg, p < 0.001) in the second month, and there was no additional mean weight loss in the sixth month of follow-up. In addition, this result seems to be independent of the patient’s insulin resistance. We did not see any serious side effects in any of the patients.

Conclusion:

Although the use of intragastric injection of BTX-A in the treatment of obesity is a controversial issue, we showed in our study that it causes significant weight loss. Further studies are needed on this subject, as it can be a safe method when the ideal dose and application site are combined with appropriate patient selection.
Combined effect of unrelated donor age and HLA peptide-binding motif match status on HCT outcomes
Authors: Mehta Rohtesh S. , Petersdorf Effie W. , Spellman Stephen R. , Lee Stephanie J.
Published: March 2024

An HLA-mismatched unrelated donor who is class I peptide-binding motif (PBM)-matched is preferred over a PBM-mismatched donor. We hypothesized that using a younger donor (aged ≤35 years vs >35 years) could compensate for the inferior overall survival (OS) associated with PBM mismatches. We compared 6 groups: HLA-matched/younger donor (n = 10 531), HLA-matched/older donor (n = 3572), PBM-matched/younger donor (n = 357), PBM-matched/older donor (n = 257), PBM-mismatched/younger donor (n = 616), and PBM-mismatched/older donor (n = 339) in patients undergoing transplantation with conventional graft-versus-host disease prophylaxis. In multivariate analysis, HLA-matched/younger donors were associated with superior OS relative to any other group. Pairwise comparisons showed that donor age significantly impacted OS in both HLA-matched and HLA-mismatched groups. Moreover, younger donors appeared to negate the detrimental effect of PBM mismatching: the PBM-matched/younger donor group had similar OS as the HLA-matched/older donor group and the PBM-mismatched/younger donor group had similar OS as the PBM-matched/older donor group. Our study suggests that older unrelated donor age and PBM mismatching confer similarly adverse effects on OS and the impacts are additive, a finding which may widen the “acceptable” donor pool. The best OS is observed with HLA-matched/younger donors and the worst with PBM-mismatched/older donors. These findings should be validated with other data sets and with posttransplantation cyclophosphamide-based prophylaxis.
The glymphatic system in migraine and other headaches
Authors: Vittorini Maria Grazia , Sahin Aysenur , Trojan Antonin , Yusifli Sevil , Alashvili Tamta , Bonifácio Gonçalo V. , Paposhvili Ketevan , Tischler Viktoria , Lampl Christian , Sacco Simona ,   on behalf of the School of Advanced Studies of the European Headache Federation (EHF-SAS)
Published: March 2024

Glymphatic system is an emerging pathway of removing metabolic waste products and toxic solutes from the brain tissue. It is made of a network of perivascular spaces, filled in cerebrospinal and interstitial fluid, encompassing penetrating and pial vessels and communicating with the subarachnoid space. It is separated from vessels by the blood brain barrier and from brain tissue by the endfeet of the astrocytes rich in aquaporin 4, a membrane protein which controls the water flow along the perivascular space. Animal models and magnetic resonance (MR) studies allowed to characterize the glymphatic system function and determine how its impairment could lead to numerous neurological disorders (e.g. Alzheimer’s disease, stroke, sleep disturbances, migraine, idiopathic normal pressure hydrocephalus). This review aims to summarize the role of the glymphatic system in the pathophysiology of migraine in order to provide new ways of approaching to this disease and to its therapy.
Intravenous cyclophosphamide therapy for patients with severe ocular inflammatory diseases who failed other immunomodulatory therapies
Authors: Karaca Irmak , Tran Elaine M. , Park SungWho , Bromeo Albert , Khojasteh Hassan , Tran Anh Ngọc Tram , Yavari Negin , Akhavanrezayat Amir , Yasar Cigdem , Uludag Kirimli Gunay , Than Ngoc Tuong Trong , Hassan Muhammad , Or Christopher , Ghoraba Hashem , Do Diana V. , Nguyen Quan Dong
Published: March 2024

Background

Ocular inflammatory diseases, including scleritis and uveitis, have been widely treated with immunomodulatory therapies (IMTs) as a steroid-sparing approach. Such strategy includes conventional therapies (antimetabolites, alkylating agents, and calcineurin inhibitors) as well as biologic agents like adalimumab, infliximab, rituximab, and tocilizumab. Cyclophosphamide (CP) is an alkylating agent and mainly inhibits the functioning of both T and B cells. Though known to have potential adverse events, including bone marrow suppression, hemorrhagic cystitis, and sterility, CP has been shown to be efficacious, especially in recalcitrant cases and when used intravenous (IV) for a limited period.

Main findings

We conducted a retrospective case-series to assess the safety and efficacy of CP therapy for patients with severe ocular inflammatory diseases who failed other IMTs. Medical records of 1295 patients who presented to the Uveitis Clinic at the Byers Eye Institute at Stanford between 2017 and 2022 were reviewed. Seven patients (10 eyes) who received CP therapy for ocular inflammatory diseases with at least one year of follow-up were included. The mean age of the patients (4 males, 3 females) was 61.6 ± 14.9 (43.0–89.0) years. Clinical diagnoses included necrotizing scleritis (5 eyes), peripheral ulcerative keratitis (2 eyes), orbital pseudotumor (1 eye), HLA-B27 associated panuveitis and retinal vasculitis (2 eyes). Ocular disease was idiopathic in 3 patients, and was associated with rheumatoid arthritis, IgG-4 sclerosing disease, dermatomyositis, and ankylosing spondylitis in 1 patient each. All the patients had history of previous IMT use including methotrexate (5), mycophenolate mofetil (3), azathioprine (1), tacrolimus (1), adalimumab (2), infliximab (4), and rituximab (1). The mean follow-up time was 34.4 ± 11.0 (13–45) months, and mean duration of CP therapy was 11.9 ± 8.8 (5–28) months. Remission was achieved in 5 patients (71.4%). Four patients (57.1%) experienced transient leukopenia (white blood cell count < 4000/mL).

Short conclusion

CP therapy can be considered a potentially effective and relatively safe therapeutic option for patients with severe ocular inflammatory diseases who failed other IMTs including biologics (TNFa and CD20 inhibitors).
Multi-Omics integration can be used to rescue metabolic information for some of the dark region of the Pseudomonas putida proteome
Authors: Tavis Steven , Hettich Robert L.
Published: March 2024

In every omics experiment, genes or their products are identified for which even state of the art tools are unable to assign a function. In the biotechnology chassis organismPseudomonas putida,these proteins of unknown function make up 14% of the proteome. This missing information can bias analyses since these proteins can carry out functions which impact the engineering of organisms. As a consequence of predicting protein function across all organisms, function prediction tools generally fail to use all of the types of data available for any specific organism, including protein and transcript expression information. Additionally, the release of Alphafold predictions for all Uniprot proteins provides a novel opportunity for leveraging structural information. We constructed a bespoke machine learning model to predict the function of recalcitrant proteins of unknown function inPseudomonas putidabased on these sources of data, which annotated 1079 terms to 213 proteins. Among the predicted functions supplied by the model, we found evidence for a significant overrepresentation of nitrogen metabolism and macromolecule processing proteins. These findings were corroborated by manual analyses of selected proteins which identified, among others, a functionally unannotated operon that likely encodes a branch of the shikimate pathway.
Structural and functional characterization of genes PYL-PP2C-SnRK2s in the ABA signalling pathway of Cucurbita pepo
Authors: Iglesias-Moya Jessica , Benítez Álvaro , Segura María , Alonso Sonsoles , Garrido Dolores , Martínez Cecilia , Jamilena Manuel
Published: March 2024

Background

The core regulation of the abscisic acid (ABA) signalling pathway comprises the multigenic familiesPYL,PP2C,andSnRK2. In this work, we conducted a genome-wide study of the components of these families inCucurbita pepo.

Results

The bioinformatic analysis of theC. pepogenome resulted in the identification of 19CpPYL, 102CpPP2Cand 10CpSnRK2genes. The investigation of gene structure and protein motifs allowed to define 4 PYL, 13 PP2C and 3 SnRK2 subfamilies. RNA-seq analysis was used to determine the expression of these gene families in different plant organs, as well as to detect their differential gene expression during germination, and in response to ABA and cold stress in leaves. The specific tissue expression of some gene members indicated the relevant role of some ABA signalling genes in plant development. Moreover, their differential expression under ABA treatment or cold stress revealed those ABA signalling genes that responded to ABA, and those that were up- or down-regulated in response to cold stress. A reduced number of genes responded to both treatments. SpecificPYL-PP2C-SnRK2genes that had potential roles in germination were also detected, including those regulated early during the imbibition phase, those regulated later during the embryo extension and radicle emergence phase, and those induced or repressed during the whole germination process.

Conclusions

The outcomes of this research open new research lines for agriculture and for assessing gene function in future studies.
Characterization of the broad-spectrum antibacterial activity of bacteriocin-like inhibitory substance-producing probiotics isolated from fermented foods
Authors: Thuy Tran Thi Dieu , Lu Hsu-Feng , Bregente Carl Jay Ballena , Huang Fong-Chi Annabelle , Tu Pei-Chun , Kao Cheng-Yen
Published: March 2024

Antimicrobial peptides, such as bacteriocin, produced by probiotics have become a promising novel class of therapeutic agents for treating infectious diseases. Selected lactic acid bacteria (LAB) isolated from fermented foods with probiotic potential were evaluated for various tests, including exopolysaccharide production, antibiotic susceptibility, acid and bile tolerance, antibacterial activity, and cell adhesion and cytotoxicity to gastric cell lines. Six selected LAB strains maintained their high viability under gastrointestinal conditions, produced high exopolysaccharides, showed no or less cytotoxicity, and adhered successfully to gastric cells. Furthermore, three strains, Weissella confusa CYLB30, Lactiplantibacillus plantarum CYLB47, and Limosilactobacillus fermentum CYLB55, demonstrated a strong antibacterial effect against drug-resistant Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella enterica serovar Choleraesuis, Enterococcus faecium, and Staphylococcus aureus. Whole genome sequencing was performed on these three strains using the Nanopore platform; then, the results showed that all three strains did not harbor genes related to toxins, superantigens, and acquired antimicrobial resistance, in their genome. The bacteriocin gene cluster was found in CYLB47 genome, but not in CYLB30 and CYLB55 genomes. In SDS-PAGE, the extract of CYLB30 and CYLB47 bacteriocin-like inhibitory substance (BLIS) yielded a single band with a size of less than 10 kDa. These BLIS inhibited the growth and biofilm formation of drug-resistant P. aeruginosa and methicillin-resistant S. aureus (MRSA), causing membrane disruption and inhibiting adhesion ability to human skin HaCaT cells. Moreover, CYLB30 and CYLB47 BLIS rescued the larvae after being infected with P. aeruginosa and MRSA infections. In conclusion, CYLB30 and CYLB47 BLIS may be potential alternative treatment for multidrug-resistant bacteria infections.
Text analysis framework for identifying mutations among non-small cell lung cancer patients from laboratory data
Authors: Yusuf Amman , Boyne Devon J. , O’Sullivan Dylan E. , Brenner Darren R. , Cheung Winson Y. , Mirza Imran , Jarada Tamer N.
Published: March 2024

Background

Laboratory data can provide great value to support research aimed at reducing the incidence, prolonging survival and enhancing outcomes of cancer. Data is characterized by the information it carries and the format it holds. Data captured in Alberta’s biomarker laboratory repository is free text, cluttered and rouge. Such data format limits its utility and prohibits broader adoption and research development. Text analysis for information extraction of unstructured data can change this and lead to more complete analyses. Previous work on extracting relevant information from free text, unstructured data employed Natural Language Processing (NLP), Machine Learning (ML), rule-based Information Extraction (IE) methods, or a hybrid combination between them.

Methods

In our study, text analysis was performed on Alberta Precision Laboratories data which consisted of 95,854 entries from the Southern Alberta Dataset (SAD) and 6944 entries from the Northern Alberta Dataset (NAD). The data covers all of Alberta and is completely population-based. Our proposed framework is built around rule-based IE methods. It incorporates topics such as Syntax and Lexical analyses to achieve deterministic extraction of data from biomarker laboratory data (i.e., Epidermal Growth Factor Receptor (EGFR) test results). Lexical analysis compromises of data cleaning and pre-processing, Rich Text Format text conversion into readable plain text format, and normalization and tokenization of text. The framework then passes the text into the Syntax analysis stage which includes the rule-based method of extracting relevant data. Rule-based patterns of the test result are identified, and a Context Free Grammar then generates the rules of information extraction. Finally, the results are linked with the Alberta Cancer Registry to support real-world cancer research studies.

Results

Of the original 5512 entries in the SAD dataset and 5017 entries in the NAD dataset which were filtered for EGFR, the framework yielded 5129 and 3388 extracted EGFR test results from the SAD and NAD datasets, respectively. An accuracy of 97.5% was achieved on a random sample of 362 tests.

Conclusions

We presented a text analysis framework to extract specific information from unstructured clinical data. Our proposed framework has shown that it can successfully extract relevant information from EGFR test results.
Factors associated with family planning use among refugee and host populations in Adjumani district, West Nile, Uganda: a comparative study
Authors: Achola Roselline , Atuyambe Lynn , Nabiwemba Elizabeth , Fredrick Makumbi , Orach Christopher Garimoi
Published: March 2024

Introduction

Uganda currently hosts an estimated 1.5 million refugees. The refugees have challenges in accessing family planning (FP) services in the host country. The study aimed to investigate factors associated with FP use among host and refugee populations in Adjumani district, Uganda.

Methods

A comparative cross-sectional study was conducted in May 2021 in three refugee settlements and their host communities in Adjumani district. A total of 1,310 respondents, (664 refugees and 646 host) were randomly selected using multistage cluster sampling and interviewed. Quantitative data were collected using structured questionnaires and analyzed using STATA V.15. Descriptive and Multivariate analysis performed.

Results

We found that modern Contraceptive Prevalence Rate (mCPR) was 30.2% (32.2% for host and 28.2% for refugees). Multivariate analysis showed that women who live singly (AOR = 2.25, 95%, CI: 1.56 -3.84), completed primary education [AOR = 1.65, 95% CI: 1.27–2.16], acquired skills [AOR = 2.28, 95% CI: 2.11–2.47], have the desire for another child [AOR = 3.73, 95% CI: 1.45- 9.60], have stayed in the study area between 3–5 years [AOR = 2.24, 95% CI: 1.46–3.42] were statistically significantly associated with FP use among both refugee and host populations. The key barrier to FP use by host was harassment of women and separation/divorce for not consulting the family members. Whereas amongst the refugees, they do not want to use FP methods.

Conclusion

Our findings revealed low FP use amongst both populations in Adjumani district. The main factors associated with FP use amongst refugee populations included marital status, level of education, type of occupation, and duration of stay in the study area whereas amongst the host is the marital status. Main reasons for not using FP methods included fear of side effects by hosts and not wanting to use FP by refugees. There is need to sensitize both communities about the benefits of FP at community level.
Traditionally removed mandibular central incisors and oral health-related quality of life: a cross-sectional study among adolescents in Maasai populated areas, Northern Tanzania
Authors: Simangwa Lutango D , Åstrøm Anne N , Johansson Anders , Minja Irene K , Johansson Ann-Katrin
Published: March 2024

Background

The traditional removal of mandibular anterior teeth has been existing for many years in the Sub-Saharan African countries. This study aimed to assess the prevalence and sociodemographic distribution of traditionally removed mandibular central incisors (TRMCI) and its association with oral impact on daily performance (OIDP) among adolescents in Maasai populated areas in the Northern part of Tanzania.

Methods

Using a two-stage cluster sample design, with schools as the primary sampling unit, 23 out of 66 eligible rural schools were randomly selected. From each selected school, one class, expected to contain adolescents aged 12–14 years, was identified. The students from these selected classes were invited to participate in the study. A total of 989 adolescents were invited and 906 (91.6%) accepted to participate and completed both an interview and a clinical oral examination.

Results

Mean age was 13.4 years (12–17 years, SD 1.2) and 43.9% were males (n = 398). The participants from Longido district amounted to 47.1%. The Maasai group constituted 79.6% of the study participants. The frequency of the participants missing at least one mandibular central incisor were 18.5%. Multivariable logistic regression revealed that adolescents from Longido district were more likely to report at least one TRMCI (OR = 2.5, 95% CI 1.4–3.3). Adolescents from non-Maasai group were less likely to have atleast one TRMCI compared to adolescents from Maasai ethnic group (OR = 0.02, 95% CI 0.002–0.15). Adolescents with at least one TRMCI were more likely to report impacts on OIDP (OR = 3.3, 95% CI 1.9–5.7) than those without TRMCI. Independent of the TRMCI status, adolescents from Longido district were less likely than their counterparts to report oral impacts (OR = 0.4, 95% CI 0.2–0.6). Similarly, adolescents from non-Masaai group were more likely than their counterparts to report oral impacts (OR = 2.2, 95% CI 1.4–3.5).

Conclusion

TRMCI is common among adolescents in the Maasai populated areas in the Northern part of Tanzania and strongly associated with the district of residence and Maasai ethnicity and has a negative impact on oral health related quality of life. There is a need for oral health education in the rural Maasai communities in Tanzania to increase awareness of the negative consequences of this practice.
Effects of intratesticular injection of hypertonic mannitol and saline on the quality of donkey sperm, indicators of oxidative stress and testicular tissue pathology
Authors: Baqerkhani Mohammadreza , Soleimanzadeh Ali , Mohammadi Rahim
Published: March 2024

Objectives

The aim of the present study was to examine donkey sperm quality after intratesticular injection of hypertonic mannitol (HM) and saline (HS).

Methods

Randomly assigned to five treatment groups were 15 adult male donkeys: (1) Control group (no treatment), (2) Surgery group (surgical castration for testosterone control), (3) NS group (normal saline intratesticular injection), (4) HS group (hypertonic saline), and (5) HM group. We injected 20 mL per testicle. We took 5 mL blood from all donkeys before injection. Castration was performed under general anesthesia 60 days later. Samples included blood and testicular tissue. Total motility (TM), progressive motility (PM), movementy features, DNA damage, morphology, viability, and plasma membrane functionality were evaluated. Hormone analyses, histomorphometric studies and oxidative stress indices including total antioxidant capacity (TAC), glutathione peroxidase (GPx), glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), and NADP+/NADPH were evaluated. Apoptosis, pyroptosis-related Bax, Caspase-1, GSDMD, and Bcl-2 expression were also assessed.

Results

In HS and HM groups, testosterone, epididymal sperm count, motility, viability, and plasma membrane functionality dropped while sperm DNA damage increased. HS and HM groups had significantly lower histomorphometric parameters, TAC, GPx, SOD, GSH, and Bcl-2 gene expression. MDA, NADP+/NADPH, Bax, Caspase-1, and GSDMD gene expression were substantially higher in the HS and HM groups than in the control group.

Conclusions

Toxic effects of hypertonic saline and mannitol on reproductive parameters were seen following, hence, they might be considered as a good chemical sterilizing treatment in donkeys.
Decoding contextual crosstalk: revealing distinct interactions between non-coding RNAs and unfolded protein response in breast cancer
Authors: Karamali Negin , Daraei Arshia , Rostamlou Arman , Mahdavi Roya , Akbari Jonoush Zahra , Ghadiri Nooshin , Mahmoudi Zahra , Mardi Amirhossein , Javidan Moslem , Sohrabi Sepideh , Baradaran Behzad
Published: March 2024

Breast cancer is significantly influenced by endoplasmic reticulum (ER) stress, impacting both its initiation and progression. When cells experience an accumulation of misfolded or unfolded proteins, they activate the unfolded protein response (UPR) to restore cellular balance. In breast cancer, the UPR is frequently triggered due to challenging conditions within tumors. The UPR has a dual impact on breast cancer. On one hand, it can contribute to tumor growth by enhancing cell survival and resistance to programmed cell death in unfavorable environments. On the other hand, prolonged and severe ER stress can trigger cell death mechanisms, limiting tumor progression. Furthermore, ER stress has been linked to the regulation of non-coding RNAs (ncRNAs) in breast cancer cells. These ncRNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), play essential roles in cancer development by influencing gene expression and cellular processes. An improved understanding of how ER stress and ncRNAs interact in breast cancer can potentially lead to new treatment approaches. Modifying specific ncRNAs involved in the ER stress response might interfere with cancer cell survival and induce cell death. Additionally, focusing on UPR-associated proteins that interact with ncRNAs could offer novel therapeutic possibilities. Therefore, this review provides a concise overview of the interconnection between ER stress and ncRNAs in breast cancer, elucidating the nuanced effects of the UPR on cell fate and emphasizing the regulatory roles of ncRNAs in breast cancer progression.
Factors affecting delays in seeking treatment among malaria patients during the pre-certification phase in China
Authors: Jia Lianyu , Chen Xiaoyu , Feng Zhanchun , Tang Shangfeng , Feng Da
Published: March 2024

Background

Delays in malaria treatment can not only lead to severe and even life-threatening complications, but also foster transmission, putting more people at risk of infection. This study aimed to investigate the factors influencing treatment delays among malaria patients and their health-seeking behaviour.

Methods

The medical records of 494 patients diagnosed with malaria from 6 different malaria-endemic provinces in China were analysed. A bivariate and multivariable regression model was used to investigate the association between delays in seeking treatment and various factors. A Sankey diagram was used to visualize the trajectories of malaria patients seeking medical care. Total treatment delays were categorized as patient delays and doctor delays.

Results

The incidence of total delays in seeking malaria treatment was 81.6%, of which 28.4% were delayed by patients alone and 34.8% by doctors alone. The median time from the onset of symptoms to the initial healthcare consultation was 1 day. The median time from the initial healthcare consultation to the conclusive diagnosis was 2 day. After being subjected to multiple logistic regression analysis, living in central China was less likely to experience patient delays (OR = 0.43, 95% CI 0.24–0.78). The factors significantly associated with the lower likelihood of doctor delays included: age between 30 to 49 (OR = 0.43, 95% CI 0.23–0.81), being single/divorce/separated (OR = 0.48, 95% CI 0.24–0.95), first visiting a county-level health institution (OR = 0.25, 95% CI 0.14–0.45), first visiting a prefectural health institution (OR = 0.06, 95% CI 0.03–0.12) and first visiting a provincial health institution (OR = 0.05, 95%CI 0.02–0.12). Conversely, individuals with mixed infections (OR = 2.04, 95% CI 1.02–4.08) and those experiencing periodic symptoms (OR = 1.71, 95% CI 1.00–2.92) might face increased doctor delays. Furthermore, higher financial burden and complications were found to be associated with patient delays. Doctor delays, in addition to incurring these two consequences, were associated with longer hospital stays.

Conclusion

There was a substantial delay in access to health care for malaria patients before China was certified malaria free. Region, marital status, periodic symptoms and the level of health institutions were factors contributing to delays in treatment-seeking among malaria patients.
Intrinsic capacity trajectories and socioeconomic inequalities in health: the contributions of wealth, education, gender, and ethnicity
Authors: Salinas-Rodríguez Aaron , Fernández-Niño Julián Alfredo , Rivera-Almaraz Ana , Manrique-Espinoza Betty
Published: March 2024

Background

Life-long health inequalities exert enduring impacts and are governed by social determinants crucial for achieving healthy aging. A fundamental aspect of healthy aging, intrinsic capacity, is the primary focus of this study. Our objective is to evaluate the social inequalities connected with the trajectories of intrinsic capacity, shedding light on the impacts of socioeconomic position, gender, and ethnicity.

Methods

Our dynamic cohort study was rooted in three waves (2009, 2014, 2017) of the World Health Organization’s Study on Global AGEing and Adult Health in Mexico. We incorporated a nationally representative sample comprising 2722 older Mexican adults aged 50 years and over. Baseline measurements of socioeconomic position, gender, and ethnicity acted as the exposure variables. We evaluated intrinsic capacity across five domains: cognition, psychological, sensory, vitality, and locomotion. The Relative Index of Inequality and Slope Index of Inequality were used to quantify socioeconomic disparities.

Results

We discerned three distinct intrinsic capacity trajectories: steep decline, moderate decline, and slight increase. Significant disparities based on wealth, educational level, gender, and ethnicity were observed. Older adults with higher wealth and education typically exhibited a trajectory of moderate decrease or slight increase in intrinsic capacity. In stark contrast, women and indigenous individuals were more likely to experience a steeply declining trajectory.

Conclusions

These findings underscore the pressing need to address social determinants, minimize gender and ethnic discrimination to ensure equal access to resources and opportunities across the lifespan. It is imperative for policies and interventions to prioritize these social determinants in order to promote healthy aging and alleviate health disparities. This approach will ensure that specific demographic groups receive customized support to sustain their intrinsic capacity during their elder years.
Routine evaluation of HBV-specific T cell reactivity in chronic hepatitis B using a broad-spectrum T-cell epitope peptide library and ELISpot assay
Authors: Wu Yandan , Liu Xiaotao , Mao Yuan , Ji Ruixue , Xia Lingzhi , Zhou Zining , Ding Yan , Li Pinqing , Zhao Yu , Peng Min , Qiu Jie , Shen Chuanlai
Published: March 2024

Background

The clinical routine test of HBV-specific T cell reactivity is still limited due to the high polymorphisms of human leukocyte antigens (HLA) in patient cohort and the lack of universal detection kit, thus the clinical implication remains disputed.

Methods

A broad-spectrum peptide library, which consists of 103 functionally validated CD8+ T-cell epitopes spanning overall HBsAg, HBeAg, HBx and HBpol proteins and fits to the HLA polymorphisms of Chinese and Northeast Asian populations, was grouped into eight peptide pools and was used to establish an ELISpot assay for enumerating the reactive HBV-specific T cells in PBMCs. Totally 294 HBV-infected patients including 203 ones with chronic hepatitis B (CHB), 13 ones in acute resolved stage (R), 52 ones with liver cirrhosis (LC) and 26 ones with hepatocellular carcinoma (HCC) were detected, and 33 CHB patients were longitudinally monitored for 3 times with an interval of 3–5 months.

Results

The numbers of reactive HBV-specific T cells were significantly correlated with ALT level, HBsAg level, and disease stage (R, CHB, LC and HCC), and R patients displayed the strongest HBV-specific T cell reactivity while CHB patients showed the weakest one. For 203 CHB patients, the numbers of reactive HBV-specific T cells presented a significantly declined trend when the serum viral DNA load, HBsAg, HBeAg or ALT level gradually increased, but only a very low negative correlation coefficient was defined (r = − 0.21, − 0.21, − 0.27, − 0.079, respectively). Different Nucleotide Analogs (NUCs) did not bring difference on HBV-specific T cell reactivity in the same duration of treatment. NUCs/pegIFN-α combination led to much more reactive HBV-specific T cells than NUCs monotherapy. The dynamic numbers of reactive HBV-specific T cells were obviously increasing in most CHB patients undergoing routine treatment, and the longitudinal trend possess a high predictive power for the hepatitis progression 6 or 12 months later.

Conclusion

The presented method could be developed into an efficient reference method for the clinical evaluation of cellular immunity. The CHB patients presenting low reactivity of HBV-specific T cells have a worse prognosis for hepatitis progression and should be treated using pegIFN-α to improve host T-cell immunity.
Lactation induction in a transgender woman: case report and recommendations for clinical practice
Authors: van Amesfoort Jojanneke E. , Van Mello Norah M. , van Genugten Renate
Published: March 2024

Background

We present a case of non-puerperal induced lactation in transgender woman. Medical literature on lactation induction for transgender women is scarce, and the majority of literature and protocols on lactation induction is based on research in cisgender women. Healthcare professionals may lack the precise knowledge about lactation induction and may therefore feel insecure when advice is requested. Subsequently, there is a rising demand for guidelines and support.

Methods

Patient medical record was consulted and a semi-structured interview was conducted to explore the motive for lactation induction, the experience of lactation induction, and to gather additional information about the timeline and course of events.

Case presentation

In this case a 37-year-old transgender woman, who was under the care of the centre of expertise on gender dysphoria in Amsterdam, and in 2020 started lactation induction because she had the wish to breastfeed her future infant. She was in a relationship with a cisgender woman and had been using gender affirming hormone therapy for 13 years. Prior to initiating gender affirming hormone therapy she had cryopreserved her semen. Her partner conceived through Intracytoplasmic Sperm Injection, using our patient’s cryopreserved sperm.

To induce lactation, we implemented a hormone-regimen to mimic pregnancy, using estradiol and progesterone, and a galactogogue; domperidone. Our patient started pumping during treatment. Dosage of progesterone and estradiol were significantly decreased approximately one month before childbirth to mimic delivery and pumping was increased. Our patient started lactating and although the production of milk was low, it was sufficient for supplementary feeding and a positive experience for our patient.

Two weeks after birth, lactation induction was discontinued due to suckling problems of the infant and low milk production.

Conclusions

This case report underlined that lactation induction protocols commonly used for cisgender women are also effective in transgender women. However, the amount of milk produced may not be sufficient for exclusive nursing. Nevertheless, success of induced lactation may be attributed to its importance for parent-infant bonding, rather than the possibility of exclusive chestfeeding.
APOE4 genotype and aging impair injury-induced microglial behavior in brain slices, including toward Aβ, through P2RY12
Authors: Sepulveda Jordy , Kim Jennifer Yejean , Binder Joseph , Vicini Stefano , Rebeck G. William
Published: March 2024

Microglia are highly dynamic cells that play a critical role in tissue homeostasis through the surveillance of brain parenchyma and response to cues associated with damage. Aging and APOE4 genotype are the strongest risk factors for Alzheimer’s disease (AD), but how they affect microglial dynamics remains unclear. Using ex vivo confocal microscopy, we analyzed microglial dynamic behaviors in the entorhinal cortex (EC) and hippocampus CA1 of 6-, 12-, and 21-month-old mice APOE3 or APOE4 knock-in mice expressing GFP under the CX3CR1 promoter. To study microglia surveillance, we imaged microglia baseline motility for 20 min and measured the extension and retraction of processes. We found that APOE4 microglia exhibited significantly less brain surveillance (27%) compared to APOE3 microglia in 6-month-old mice; aging exacerbated this deficit. To measure microglia response to damage, we imaged process motility in response to ATP, an injury-associated signal, for 30 min. We found APOE4 microglia extended their processes significantly slower (0.9 µm/min, p < 0.005) than APOE3 microglia (1.1 μm/min) in 6-month-old animals. APOE-associated alterations in microglia motility were observed in 12- and 21-month-old animals, and this effect was exacerbated with aging in APOE4 microglia. We measured protein and mRNA levels of P2RY12, a core microglial receptor required for process movement in response to damage. We found that APOE4 microglia express significantly less P2RY12 receptors compared to APOE3 microglia despite no changes in P2RY12 transcripts. To examine if the effect of APOE4 on the microglial response to ATP also applied to amyloid β (Aβ), we infused locally Hi-Lyte Fluor 555-labeled Aβ in acute brain slices of 6-month-old mice and imaged microglia movement for 2 h. APOE4 microglia showed a significantly slower (p < 0.0001) process movement toward the Aβ, and less Aβ coverage at early time points after Aβ injection. To test whether P2RY12 is involved in process movement in response to Aβ, we treated acute brain slices with a P2RY12 antagonist before Aβ injection; microglial processes no longer migrated towards Aβ. These results provide mechanistic insights into the impact of APOE4 genotype and aging in dynamic microglial behaviors prior to gross Aβ pathology and could help explain how APOE4 brains are more susceptible to AD pathogenesis.
The role of surgical tissue injury and intraoperative sympathetic activation in postoperative immunosuppression after breast-conserving surgery versus mastectomy: a prospective observational study
Authors: Jacobs Lotte MC , Helder Leonie S , Albers Kim I , Kranendonk Josephine , Keijzer Christiaan , Joosten Leo AB , Strobbe Luc JA , Warlé Michiel C
Published: March 2024

Background

Breast cancer is the second most common cause of death from cancer in women worldwide. Counterintuitively, large population-based retrospective trials report better survival after breast-conserving surgery (BCS) compared to mastectomy, corrected for tumour- and patient variables. More extensive surgical tissue injury and activation of the sympathetic nervous system by nociceptive stimuli are associated with immune suppression. We hypothesized that mastectomy causes a higher expression of plasma damage associated molecular patterns (DAMPs) and more intraoperative sympathetic activation which induce postoperative immune dysregulation. Immune suppression can lead to postoperative complications and affect tumour-free survival.

Methods

In this prospective observational study, plasma DAMPs (HMGB1, HSP70, S100A8/A9 and S100A12), intraoperative sympathetic activation (Nociception Level (NOL) index from 0 to 100), and postoperative immune function (plasma cytokine concentrations and ex vivo cytokine production capacity) were compared in patients undergoing elective BCS (n = 20) versus mastectomy (n = 20).

Results

Ex vivo cytokine production capacity of TNF, IL-6 and IL-1β was nearly absent in both groups one hour after surgery. Levels appeared recovered on postoperative day 3 (POD3), with significantly higher ex vivo production capacity of IL-1β after BCS (p = .041) compared to mastectomy. Plasma concentration of IL-6 was higher one hour after mastectomy (p = .045). Concentrations of plasma alarmins S100A8/A9 and S100A12 were significantly higher on POD3 after mastectomy (p = .003 and p = .041, respectively). Regression analysis showed a significantly lower percentage of NOL measurements ≤ 8 (absence of nociception) during mastectomy when corrected for norepinephrine equivalents (36% versus 45% respectively, p = .038). Percentage of NOL measurements ≤ 8 of all patients correlated with ex vivo cytokine production capacity of IL-1β and TNF on POD3 (r = .408; p = .011 and r = .500; p = .001, respectively).

Conclusions

This pilot study revealed substantial early postoperative immune suppression after BCS and mastectomy that appears to recover in the following days. Differences between BCS and mastectomy in release of DAMPs and intraoperative sympathetic activation could affect postoperative immune homeostasis and thereby contribute to the better survival reported after BCS in previous large population-based retrospective trials. These results endorse further exploration of (1) S100 alarmins as potential therapeutic targets in breast cancer surgery and (2) suppression of intraoperative sympathetic activation to substantiate the observed association with postoperative immune dysregulation.
EFFects of Exposure and Cognitive behavioral Therapy for chronic BACK pain (“EFFECT-BACK”): study protocol for a randomized controlled trial
Authors: Vogt Rabea , Haas Julia , Baumann Lukas , Sander Anja , Klose Christina , Riecke Jenny , Rief Winfried , Bingel Ulrike , Maser Dustin , Witthöft Michael , Keßler Jens , Zugaj Marco Richard , Ditzen Beate , Glombiewski Julia Anna
Published: March 2024

Introduction

Chronic back pain is a widespread medical condition associated with high socioeconomic costs and increasing prevalence. Despite the advanced implementation of multidisciplinary approaches, providing a satisfactory treatment offer for those affected is often not possible. Exposure therapy (EXP) promises to be an effective and economical form of treatment and in a previous pilot study showed to be superior to cognitive behavioral therapy (CBT) in reducing perceived limitations of movement. The current study aims to further compare the efficacy of both treatment methods and identify those patient groups that particularly benefit from EXP.

Methods

The general objective of this randomized multicenter clinical trial (targeted N = 380) is to improve and expand the range of treatments available to patients with chronic back pain. As the primary objective of the study, two different psychological treatments (EXP and CBT) will be compared. The primary outcome measure is a clinically significant improvement in pain-related impairment, measured by the QPBDS, from baseline to 6-month follow-up. Secondary outcome measures are absolute changes and clinically significant improvements in variables coping, psychological flexibility, depressiveness, catastrophizing, exercise avoidance and fear of exercise, and intensity of pain. Participants are recruited in five psychological and medical centers in Germany and receive ten sessions of manualized therapy by trained licensed CBT therapists or clinical psychologists, who are currently in their post-gradual CBT training. Potential predictors of each treatment’s efficacy will be explored with a focus on avoidance and coping behavior.

Conclusion

This study will be the first RCT to compare CBT and EXP in chronic back pain in a large sample, including patients from different care structures due to psychological and medical recruitment centers. By identifying and exploring potential predictors of symptom improvement in each treatment group, this study will contribute to enable a more individualized assignment to treatment modalities and thus improves the care situation for chronic back pain and helps to create a customized treatment program for subgroups of pain patients. If our findings confirm EXP to be an efficacious and efficient treatment concept, it should gain more attention and be further disseminated.

Trial registration

ClinicalTrials.gov NCT05294081. Registered on 02 March 2022.