bluuebunny/crossref_metadata_2025 huggingface dataset:
Relapsing autoimmune inner ear disease with significant response to methotrexate and azathioprine combination therapy: A case report and mini literature review
Authors: Huang Kuan-Hsuan , Lin Hsiao-Ching , Lin Chia-Der , Wu Po-Chang
Published: June 2023

Rationale:

Autoimmune inner ear disease typically presents with bilateral hearing loss that progresses over weeks or months though its mechanisms are unknown. Corticosteroids are the first-line treatment, but their responses are variable and relapses are frequent. Thus, many experts have sought to replace corticosteroids with immunosuppressive agents.

Patient concerns:

A 35-year-old woman experienced a progressive hearing impairment, initially on the left side and later becoming bilateral. Her response to corticosteroid monotherapy was temporary, and there have been two relapse episodes over several months.

Diagnoses:

Autoimmune inner ear disease was considered due to evidence of autoimmunity combined with a clinical course of bilateral and recurrent sensorineural hearing loss and a partial response to corticosteroid therapy.

Interventions:

The patient received a 3-day mini-pulse of methylprednisolone at 250 mg/d, followed by 12 mg/d maintenance, and concurrently began an azathioprine regimen gradually increasing to 100 mg/day as a corticosteroid-sparing agent.

Outcomes:

Three weeks after immunosuppressive therapy, hearing and pure-tone audiometry improved, and after 7 weeks, methylprednisolone was tapered to 8 mg/d. The dosage was further reduced by adding methotrexate at 7.5 mg/week, resulting in a reduction to 4 mg/d as maintenance therapy after 4 weeks.

Lessons:

For patients who are unresponsive to corticosteroids or experience difficulty tolerating them, a combination therapy of methotrexate and azathioprine is recommended as a viable alternative as this regimen is well-tolerated and yields positive outcomes.
Integrative medicine using East Asian herbal medicine for inflammatory pain in patients with rheumatoid arthritis: A protocol for systematic review and meta-analysis integrated with multiple data mining for core candidate discovery
Authors: Jo Hee-Geun , Seo Jihye , Baek Eunhye , Hwang Ji-Hye , Lee Donghun
Published: June 2023

Background:

Rheumatoid arthritis is a chronic inflammatory autoimmune disease characterized by a wide range of clinical symptoms affecting various bodily functions, including skeletal, vascular, metabolic, and cognitive functions. This review aimed to evaluate the efficacy and safety of integrative medicine (East Asian herbal medicine combined with conventional medicine) used for the treatment of inflammatory pain in rheumatoid arthritis and to identify key candidate drugs based on the data.

Methods:

A comprehensive literature search will be conducted in 4 core databases (PubMed, Excerpta Medica database, Cochrane Library, and Cumulative Index to Nursing & Allied Health Literature) 4 Korean databases (Oriental Medicine Advanced Searching Integrated System, Korean Studies Information Service System, Research Information Service System, and Korea Citation Index), 2 Chinese databases (Chinese National Knowledge Infrastructure Database and Wanfang data), and 1 Japanese database (Citation Information by National Institute of Informatics) for randomized controlled trials from December 13, 2022. Statistical analysis will be performed using R version 4.1.2 and R Studio program. The American College of Rheumatology 20/50/70 score and rate of adverse events will be the primary outcomes. All outcomes will be analyzed using a random-effects model to produce more statistically conservative results. Sensitivity, meta-regression, and subgroup analyses will be used to identify the sources of any heterogeneity in the study. The revised tool for assessing the risk of bias in randomized trials, version 2.0, will be used to evaluate methodological quality. The overall quality of evidence will be assessed according to the Grading of Recommendations Assessment, Development, and Evaluation Pro Framework.

Ethics and dissemination:

There are no ethical issues, as no primary data will be collected directly from the participants. The results of this review will be reported in a peer-reviewed scientific journal.

Trial registration:

PROSPERO registration number: CRD42023412385.
Impact of surgical resection on the survival in Mexican patients with gastric cancer: A meta-analysis and systematic review
Authors: Gutiérrez-Solis Ana Ligia , Pacheco-Can Oscar Daniel , Vázquez-Segura Hayde Sara Leticia , Pech-Aguilar Alfredo Geovanny , Franco-González Carlos David , Avila-Nava Azalia , Lugo Roberto
Published: June 2023

Background:

Gastric cancer (GC) is one of the most frequent cancer types in Mexico. The primary method used as a treatment is surgical resection. The role of surgery in increasing survival is controversial. This study aimed to determine whether surgical resection increases the survival of patients with GC in a Mexican population.

Methods:

A systematic review of literature searches (Evidence-based MEDLINE/PubMed, Web of Science, Cochrane Library, and SciELO) and meta-analysis were performed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis criteria. The published articles from 2000 to the current time were divided into cross-sectional and randomized studies. The inclusion criteria were survival, surgical resections, patients treated in Mexico, and primary GC. The effect estimation was calculated using the risk ratio (RR). The random-effects model and a confidence interval (CI) of 95% were used.

Results:

The RR of the pooled studies was 1.09 (95% CI, 0.71–1.67). RR of 0.82 (95% CI, 0.63–1.07) was obtained in cross-sectional studies, and randomized studies showed a RR of 2.08 (95% CI, 0.25–17.07).

Conclusion:

This work is the first systematic study that assesses the role of surgery on the survival of patients with GC in the Mexican population, the results showed that surgical resection did not improve survival in patients with GC.
Coping strategy for work-family conflict and burnout in construction industrial adult workers: A philosophical highlight
Authors: Okereke Godwin Keres Okoro , Ede Moses Onyemaechi , Adejo Ode Ogbole , Nwadi Lebechukwu Calister , Oneli Joy Obiageli , Nwahunanya Innocent , Kontei Ebiegberi , Oguejiofor Ikechukwu Victor , Nkemjika Ogechi , Okereke Joy Anuri , Iliya John , Udogu Kingsley , Ike Joshua Onyekachi , Areji Anthony
Published: June 2023

Background:

The work environment in Nigeria is demanding and could lead to psychological disturbances. Evidentially, construction workers have confirmed the horrible job stress and work-family conflict they experience in the workplace. This has led to work-related burnout. As a matter of importance, this study was conducted.

Methods:

A pure experimental design was used, which helped to randomly assigned recruited 98 construction industry adult workers to 2 arms (treatment and waitlisted control groups). Two dependent measures were distributed before, immediately after, and 4 weeks after completion of intervention with 12 sessions that were given to the treatment group.

Results:

This study found that cognitive behavior therapy is beneficial in the management of work-family conflict and work burnout among construction industry workers. Therefore, there is a need for advancement and adequate implementation of cognitive behavior therapy in industries for psychological functioning of workers.
Neurokinin 1/3 receptor antagonists for menopausal women: A current systematic review and insights into the investigational non-hormonal therapy
Authors: Hassan Fatima , Saleem Anam , Samuel Sehar Saba , Sarfraz Zouina , Sarfraz Azza , Sarfraz Muzna , KC Manish
Published: June 2023

Background:

Over 75% of menopausal women experience vasomotor symptoms (VMS), such as night sweats and hot flashes. Despite the prevalence of these symptoms, there is limited data on non-hormonal therapies to alleviate them.

Methods:

PubMed, Cochrane, Scopus, Ovid, Web of Science, and ClinicalTrials.Gov were searched for relevant studies. The search was performed using the following keywords, which were customized to suit the specific databases/registers: menopause, women, neurokinin 3, and/or Fezolinetant. The search was conducted until December 20, 2022. This systematic review was conducted in compliance with the PRISMA Statement 2020 guidelines.

Results:

A total of 326 records were found, with 10 studies (enrolling 1993 women) selected for inclusion. The women received 40-mg doses of NK1/3 receptor antagonists twice daily, with follow-ups at 1 to 3 weeks. Moderately strong evidence was found suggesting that NK1/3 receptor antagonists can help limit the frequency and severity of hot flashes in menopausal women.

Conclusion:

While the results should be interpreted with caution until further clinical trials validate the efficacy and safety of NK1/3 receptor antagonists among menopausal women, these findings suggest that they are promising targets for future pharmacological and clinical studies in addressing vasomotor symptoms.
Feasibility and learning curve for robotic surgery in a small hospital: A retrospective cohort study
Authors: Shima Takafumi , Arita Asami , Sugimoto Satoshi , Takayama Shoichi , Yamamoto Masashi , Lee Sang-Woong , Okuda Junji
Published: June 2023

Robotic surgery rates, typified by the use of the da Vinci Surgical System, have increased in recent years. However, robotic surgery is mostly performed in large hospitals and has not been fully implemented in small hospitals. Therefore, we aimed to verify the feasibility of robotic surgery in small hospitals and verify the number of cases in which perioperative preparation for robotic surgery is stable by creating a learning curve in small hospitals. Forty robot-assisted rectal cancer surgeries performed in large and small hospitals by a surgeon with extensive experience in robotic surgery were validated. Draping and docking times were recorded as perioperative preparation times. Unexpected surgical interruptions, intraoperative adverse events, conversion to laparoscopic or open surgery, and postoperative complications were recorded. Cumulative sum analysis was used to derive the learning curve for perioperative preparation time. Draping times were significantly longer in the small hospital group (7 vs 10 minutes, P = .0002), while docking times were not significantly different (12 vs 13 minutes, P = .098). Surgical interruptions, intraoperative adverse events, and conversions were not observed in either group. There were no significant differences in the incidence of severe complications (25% [5/20] vs 5% [1/20], P = .184). In the small hospital group, phase I of the draping learning curve was completed in 4 cases, while phase I of the docking learning curve was completed in 7 cases. Robotic surgery is feasible for small hospitals, and the preoperative preparation time required for robotic surgery stabilizes relatively early.
Fibrosing Colonopathy Presenting in a Patient with Cystinosis
Authors: Fiore Dominic , Sohini Vidhur , Mileti Elizabeth , Fiore Nicholas
Published: June 2023

Fibrosing colonopathy is a unique pathology characterized by long segment stricture, usually of the ileocecal region. Historically, it is most commonly described in patients with cystic fibrosis (CF). Fibrosing colonopathy is felt to be secondary to excessive doses of exogenous lipase medication. This condition is rarely seen in the last decade. In this case presentation, fibrosing colonopathy was identified in a patient with the lysosomal storage disorder of cystinosis. Fibrosing colonopathy has not previously been described in patients with cystinosis. The patient was found to have fibrosing colonopathy after perforation of the colon during a colonoscopy for bloody diarrhea. This case report aims to draw attention to a noteworthy case of fibrosing colonopathy in a patient who does not have cystic fibrosis, but rather cystinosis.
Immunized Patients Face Reduced Access to Transplantation in the Eurotransplant Kidney Allocation System
Authors: de Ferrante Hans , Smeulders Bart , Tieken Ineke , Heidt Sebastiaan , Haasnoot Geert W. , Claas Frans H.J. , Vogelaar Serge , Spieksma Frits
Published: June 2023

Background.

The presence of donor-specific HLA antibodies before transplantation is associated with poor transplantation outcomes. Unacceptable antigens can be assigned for Eurotransplant kidney transplant candidates to prevent kidney offers against which the candidate has developed clinically relevant HLA antibodies. This retrospective cohort study aimed to assess to what degree unacceptable antigens affect access to transplantation in the Eurotransplant Kidney Allocation System (ETKAS).

Methods.

Candidates who underwent kidney-only transplantation between 2016 and 2020 were included (n = 19 240). Cox regression was used to quantify the relationship between the relative transplantation rate and virtual panel-reactive antibodies (vPRAs), which is the percentage of the donor pool with unacceptable antigens. Models used accrued dialysis time as the timescale; were stratified by country and blood group of patient and were adjusted for nontransplantable status, patient age, sex, history of kidney transplantations, and prevalence of 0 HLA-DR–mismatched donors.

Results.

Transplantation rates were 23% lower for vPRA 0.1% to 50%, 51% lower for vPRA 75% to 85%, and decreased rapidly for vPRA of >85%. Prior studies showed significantly lower ETKAS transplantation rates only for highly sensitized patients (vPRA of >85%). The inverse relationship between transplantation rate and vPRA is independent of Eurotransplant country, listing time, and 0 HLA-DR–mismatched donor availability. Results were similar when quantifying the relationship between vPRA and attainment of a sufficiently high rank for an ETKAS offer, suggesting lower transplantation rates for immunized patients are due to current ETKAS allocation.

Conclusions.

Immunized patients face lower transplantation rates across Eurotransplant. The current ETKAS allocation mechanism inadequately compensates immunized patients for reduced access to transplantation.
Sociodemographic Variables in Canadian Organ Donation Organizations: A Health Information Survey
Authors: Leeies Murdoch , Ho Julie , Wilson Lindsay C. , Lalani Jehan , James Lee , Carta Tricia , Gruber Jackie , Shemie Sam D. , Hrymak Carmen
Published: June 2023

Background.

Health systems must collect equity-relevant sociodemographic variables to measure and mitigate health inequities. The specific variables collected by organ donation organizations (ODOs) across Canada, variable definitions, and processes of the collection are not defined. We undertook a national health information survey of all ODOs in Canada. These results will inform the development of a standard national dataset of equity-relevant sociodemographic variables.

Methods.

We conducted an electronic, self-administered cross-sectional survey of all ODOs in Canada from November 2021 to January 2022. We targeted key knowledge holders familiar with the data collection processes within each Canadian ODO known to Canadian Blood Services. Categorical item responses are presented as numbers and proportions.

Results.

We achieved a 100% response rate from 10 Canadian ODOs. Most data were collected by organ donation coordinators. Only 2 of 10 ODOs reported using scripts explaining why sociodemographic data are being collected or incorporated training in cultural sensitivity for any given variable. A lack of cultural sensitivity training was endorsed by 50% of respondents as a barrier to the collection of sociodemographic variables by ODOs, whereas 40% of respondents identified a lack of training in sociodemographic variable collection as a significant barrier.

Conclusions.

Few programs routinely collect sufficient data to examine health inequities with an intersectional lens. Most data collection occurs midway through the ODO interaction, creating a missed opportunity to better understand differences in social identities of patients who register their intention to donate in advance or who decline the donation. National standardization of equity-relevant data collection definitions and processes of the collection is needed.
Impact of Perioperative Prophylaxis With Enterococcus Activity on Risk of Surgical-Site Infection After Pancreas Transplantation
Authors: Yetmar Zachary A. , McCord Molly , Lahr Brian D. , Kudva Yogish C. , Seville Maria Teresa , Bosch Wendelyn , Lemke Adley , Katariya Nitin N. , Reddy Kunam S. , Perry Dana K. , Huskey Janna L. , Jarmi Tambi , Kukla Aleksandra , Dean Patrick G. , Bernard Stacy A. , Beam Elena
Published: June 2023

Background.

Surgical-site infection (SSI) is the most common early infectious complication after pancreas transplantation (PT). Although SSI has been shown to worsen outcomes, little data exist to guide optimal choices in perioperative prophylaxis.

Methods.

We performed a retrospective cohort study of PT recipients from 2010–2020 to examine the effect of perioperative antibiotic prophylaxis with Enterococcus coverage. Enterococcus coverage included antibiotics that would be active for penicillin-susceptible Enterococcus isolates. The primary outcome was SSI within 30 d of transplantation, and secondary outcomes were Clostridioides difficile infection (CDI) and a composite of pancreas allograft failure or death. Outcomes were analyzed by multivariable Cox regression.

Results.

Of 477 PT recipients, 217 (45.5%) received perioperative prophylaxis with Enterococcus coverage. Eighty-seven recipients (18.2%) developed an SSI after a median of 15 d from transplantation. In multivariable Cox regression analysis, perioperative Enterococcus prophylaxis was associated with reduced risk of SSI (hazard ratio [HR] 0.58; 95% confidence interval [CI], 0.35-0.96; P = 0.034). Anastomotic leak was also significantly associated with elevated risk of SSI (HR 13.95; 95% CI, 8.72-22.32; P < 0.001). Overall, 90-d CDI was 7.4%, with no difference between prophylaxis groups (P = 0.680). SSI was associated with pancreas allograft failure or death, even after adjusting for clinical factors (HR 1.94; 95% CI, 1.16-3.23; P = 0.011).

Conclusions.

Perioperative prophylaxis with Enterococcus coverage was associated with reduced risk of 30-d SSI but did not seem to influence risk of 90-d CDI after PT. This difference may be because of the use of beta-lactam/beta-lactamase inhibitor combinations, which provide better activity against enteric organisms such as Enterococcus and anaerobes compared with cephalosporin. Risk of SSI was also related to anastomotic leak from surgery, and SSI itself was associated with subsequent risk of a poor outcome. Measures to mitigate or prevent early complications are warranted.
HLA Sensitization in Patients Bridged to Lung Transplantation With Extracorporeal Membrane Oxygenation
Authors: Goetz Ryan L. , Kaleekal Thomas S. , Wille Keith M. , Orozco-Hernandez Erik , Gongora Enrique , Hoopes Charles W. , Rusanov Victoria
Published: June 2023

Background.

Lung transplantation is a definitive therapy for many end-stage lung pathologies. Extracorporeal membrane oxygenation (ECMO) is increasingly being used as a bridge to lung transplantation (BTT). HLA sensitization is a major barrier to lung transplantation. The development of HLA sensitization while undergoing ECMO support as a BTT has recently been reported in a 2-patient series.

Methods.

We performed a retrospective analysis of patients undergoing ECMO as a BTT at a single large academic medical center from January 2016 to April 2022. The study was approved by the institutional review board. We selected patients who had undergone ECMO support for at least 7 d with either negative HLA before cannulation or initial negative HLA on ECMO (3 patients).

Results.

We identified 27 patients bridged to lung transplantation with available HLA data. Of this group, 8 patients (29.6%) developed significant HLA sensitization (>10%). We did not identify any factors predisposing to sensitization, including infection episodes or blood product transfusion. Sensitized patients demonstrated a trend toward an increased primary graft dysfunction rate, a need for posttransplant ECMO support, and a decreased 1-y survival; however, these did not meet statistical significance.

Conclusions.

Our study is the largest series today describing the association between HLA sensitization and ECMO therapy. We suggest that interaction between the immune system and ECMO circuit contributes to allosensitization pretransplant, similar to that occurring with ventricular assist device. Further work is needed to better characterize the incidence of HLA sensitization in a multicenter cohort and to identify potentially modifiable factors associated with HLA sensitization.
Characteristics, Risk Factors, and Outcome of New-onset Systolic Heart Failure After Liver Transplantation: A Single-center Cohort
Authors: Souki Fouad G. , Raveh Yehuda , Sancassani Rhea , Livingstone Joshua , Shatz Vadim , Ashrafi Behrouz , Shuman Miryam , Nicolau-Raducu Ramona
Published: June 2023

Background.

New-onset systolic heart failure (HF) after liver transplantation (LT) is a significant cause of morbidity and mortality; however, its characteristics are still insufficiently delineated. HF may involve the left ventricle (LV), right ventricle (RV), or both ventricles. We explored the incidence, characteristics, etiologies, risks, involved cardiac chambers, and outcomes of HF after LT.

Methods.

This study included 528 adult patients with preoperative LV ejection fraction ≥ 55% who underwent LT between 2016 and 2020. The primary outcome was new-onset systolic HF, defined by the presence of clinical signs, symptoms, and echocardiographic evidence of reduced LVejection fraction <50% and RV dysfunction within the first year after LT.

Results.

Thirty-one patients (6%) developed systolic HF within a median of 9 d (1–364). Of those, 23% of patients had ischemic HF, whereas 77% had nonischemic HF. Nonischemic HF was caused by stress (11), sepsis (8), or other factors (5). Nonischemic HF was secondary to isolated LV failure in 58% of patients or RV ± LV failure in 42% of patients. Recursive partitioning identified subgroups with varying risks and uncovered interaction between variables. HF risk increased from 4.2% to 13% when epinephrine and/or norepinephrine drips were used intraoperatively (P < 0.01). When no epinephrine and/or norepinephrine were used, HF risk increased from 3.1% to 38.5% if baseline hemoglobin was <7.2 g/dL (P < 0.01). When baseline hemoglobin was ≥7.2 g/dL, HF risk increased from 0% to 5.2% when ≥3500 mL crystalloid was used intraoperatively (P < 0.01). Posttransplant first-year survival and reversibility of HF depended on the etiology (stress, sepsis, ischemia, etc) and cardiac chamber involvement (isolated LV or RV ± LV). RV dysfunction was associated with inferior recovery of cardiac function and poorer survival than nonischemic isolated LV dysfunction (50% versus 70%, respectively).

Conclusions.

Posttransplant new-onset HF is mostly nonischemic in nature and is associated with increased morbidity and mortality.
Cytomegalovirus Immunity Assays Predict Viremia but not Replication Within the Lung Allograft
Authors: Li Jenny , Gardiner Bradley J. , Stankovic Sanda , Oates Clare V. L. , Cristiano Yvonne , Levvey Bronwyn J. , Brooks Andrew G. , Snell Gregory I. , Westall Glen P. , Sullivan Lucy C.
Published: June 2023

Background:

Cytomegalovirus (CMV) infection causes significant morbidity and mortality in lung transplant recipients. Current guidelines use pretransplant donor and recipient CMV serostatus to predict the risk of subsequent CMV replication and length of antiviral prophylaxis. Immunological monitoring may better inform the risk of CMV infection in patients, thereby allowing for improved tailoring of antiviral prophylaxis. In this study, we compared 2 commercially available assays, the QuantiFERON-CMV (QFN-CMV) and T-Track-CMV (enzyme-linked immunosorbent spot assay), to predict the risk of CMV disease in lung transplant recipients.

Methods:

We performed CMV immunity assays on 32 lung transplant recipients at risk of CMV disease as defined by serostatus (CMV-seropositive recipients, n = 26; or CMV-seronegative lung transplant recipient receiving a CMV-seropositive donor organ, n = 6). QFN-CMV and T-Track were performed on peripheral blood mononuclear cells, and episodes of CMV replication in both serum and bronchoalveolar lavage were found to be correlated to the CMV immune assays. The predictive ability of the assays was determined using Kaplan–Meier curves.

Results:

There was a degree of concordance between tests, with 44% of recipients positive for both tests and 28% negative for both tests; however, test results were discordant in 28% of cases. A negative result in either the QFN-CMV (P < 0.01) or T-Track (P < 0.05) assays was obtained in a significantly higher number of recipients who experienced CMV replication in the blood. Using these assays together gave higher predictability of CMV replication, with only 1 recipient experiencing CMV replication in the blood who obtained a positive test result for both assays. Neither assay was able to predict recipients who experienced CMV replication in the lung allograft.

Conclusions:

Our study demonstrates that CMV immunity assays can predict viremia; however, the lack of association with allograft infection suggests that CMV-specific T-cell immunity in the circulation is not associated with the control of CMV replication within the transplanted lung allograft.
Fluoroquinolone resistance does not facilitate phage Φ13 integration or excision in Staphylococcus aureus
Authors: Leinweber Helena , Sieber Raphael N. , Bojer Martin S. , Larsen Jesper , Ingmer Hanne
Published: June 2023

Prophages of the ΦSa3int family are commonly found in human-associated strains of

Staphylococcus aureus

where they encode factors for evading the human innate immune system. In contrast, they are usually absent in livestock-associated methicillin-resistant

S. aureus

(LA-MRSA) strains where the phage attachment site is mutated compared to the human strains. However, ΦSa3int phages have been found in a subset of LA-MRSA strains belonging to clonal complex 398 (CC398), including a lineage that is widespread in pig farms in Northern Jutland, Denmark. This lineage contains amino acid changes in the DNA topoisomerase IV and the DNA gyrase encoded by grlA and gyrA, respectively, which have been associated with fluoroquinolone (FQ) resistance. As both of these enzymes are involved in DNA supercoiling, we speculated that the mutations might impact recombination between the ΦSa3int phage and the bacterial chromosome. To examine this, we introduced the FQ resistance mutations into

S. aureus

8325-4attBLA
that carry the mutated CC398-like bacterial attachment site for ΦSa3int phages. When monitoring phage integration and release of Φ13, a well-described representative of the ΦSa3int phage family, we did not observe any significant differences between the FQ-resistant mutant and the wild-type strain. Thus our results suggest that mutations in grlA and gyrA do not contribute to the presence of the ΦSa3int phages in LA-MRSA CC398.
Class 1 integrons in clinical and swine industry isolates of Salmonella Typhimurium from Colombia, dating 1997 to 2017
Authors: Flórez-Delgado Nancy Yaneth , Ubillus Elizabeth Noelia , Perez-Sepulveda Blanca , Ospina-Ríos Eyda Lizeth , Carrascal-Camacho Ana Karina , Chamorro-Tobar Iliana C. , Montaño Lucy Angeline , Li Yan , Zapata-Bedoya Silvana , Hinton Jay C. D. , Villarreal José Miguel , Wiesner Magdalena
Published: June 2023

Background.

Salmonella enterica

subsp.

enterica

serovar Typhimurium (S. Typhimurium) has been linked to outbreaks of foodborne gastroenteritis disease, and the emergence of antimicrobial-resistant clones. In Colombia, laboratory surveillance of

Salmonella

spp. between 1997–2018 revealed that S. Typhimurium was the most ubiquitous serovar (27.6 % of all

Salmonella

isolates), with increasing levels of resistance to several families of antibiotics.

Hypothesis. Resistant isolates of S. Typhimurium recovered from human clinical, food and swine samples carry class 1 integrons that are linked to antimicrobial resistance genes.

Aim. Identify class 1 integrons, and investigate their association with other mobile genetic elements, and their relationship to the antimicrobial resistance of Colombian S. Typhimurium isolates.

Methods. In this study, 442 isolates of S. Typhimurium were analysed, of which 237 were obtained from blood culture, 151 from other clinical sources, 4 from non-clinical sources and 50 from swine samples. Class 1 integrons and plasmid incompatibility groups were analysed by PCR and whole-genome sequencing (WGS), and regions flanking integrons were identified by WGS. The phylogenetic relationship was established by multilocus sequence typing (MLST) and single-nucleotide polymorphism (SNP) distances for 30 clinical isolates.

Results

.
Overall, 39 % (153/392) of the human clinical isolates and 22 % (11/50) of the swine S. Typhimurium isolates carried complete class 1 integrons. Twelve types of gene cassette arrays were identified, including dfr7-aac-bla
OXA-2 (Int1-Col1), which was the most common one in human clinical isolates (75.2 %, 115/153). Human clinical and swine isolates that carried class 1 integrons were resistant to up to five and up to three antimicrobial families, respectively. The Int1-Col1 integron was most prevalent in stool isolates and was associated with Tn21. The most common plasmid incompatibility group was IncA/C.

Conclusions. The widespread presence of the IntI1-Col1 integron in Colombia since 1997 was striking. A possible relationship between integrons, source and mobile elements that favour the spread of antimicrobial resistance determinants in Colombian S. Typhimurium was identified.
Gut bacteria and sex differences in colorectal cancer
Authors: Yang Xi , Li Ping , Qu Zhanbo , Zhuang Jing , Wu Yinhang , Wu Wei , Wei Qichun
Published: June 2023

Introduction. Differences in gut bacteria that are associated with the occurrence and development of colorectal cancer (CRC) exist between sexes, and males have a higher morbidity of CRC.

Gap Statement. Clinical data for the relationship between gut bacteria and sexes in patients with CRC are not available and are needed to support individualized screening and treatment programmes.

Aim. To analyse the relationship between gut bacteria and sexes in patients with CRC.

Methodology. A total of 6 077 samples recruited by Fudan University’s Academy of Brain Artificial Intelligence Science and Technology were included, and the gut bacteria composition mainly shows the top 30 genera. Linear discriminant analysis Effect Size (LEfSe) was used to analyse the differences in gut bacteria. Pearson correlation coefficients were calculated to demonstrate the relationship of discrepant bacteria. CRC risk prediction models were used to rank the importance of valid discrepant bacteria.

Results.
Bacteroides, Eubacterium and

Faecalibacterium

were the top three bacteria in males with CRC, while Bacteroides, Subdoligranulum and

Eubacterium

were the top three bacteria in females with CRC. The abundance of gut bacteria (

Escherichia

,

Eubacteriales

, Clostridia, etc.) was higher in males with CRC compared with that in females with CRC. In addition,

Dorea

and

Bacteroides

were important CRC-related bacteria (P<0.001). Finally, the importance of discrepant bacteria was ranked based on CRC risk prediction models. Blautia, Barnesiella and

Anaerostipes

were the top three important discrepant bacteria between males with CRC and females with CRC. The value of AUC was 1.0, the sensitivity was 92.0 %, the specificity was 68.4 %, and the accuracy was 83.3 % in the discovery set.

Conclusion. Gut bacteria were correlated with sexes and CRC. It is necessary to consider gender when gut bacteria are used to treat and predict CRC.
Escherichia coli encoding Shiga toxin subtype Stx2f causing human infections in England, 2015–2022
Authors: Den Ouden Anouschka , Greig David R. , Rodwell Ella V. , Tripodo Francesco , Olonade Israel , Swift Craig , Jenkins Claire
Published: June 2023

Introduction. Shiga toxin-producing

Escherichia coli

(STEC) belong to a diverse group of gastrointestinal pathogens defined by the presence of Shiga toxin genes (stx) of which there are at least ten subtypes (Stx1a-Stx1d and Stx2a-Stx2g).

Gap Statement. Initially thought to be associated with mild symptoms, more recently STEC encoding stx2f have been isolated from cases of haemolytic uraemic syndrome (HUS) and the clinical significance and public health burden require further investigation.

Aim. We analysed clinical outcomes and genome-sequencing data linked to patients infected with STEC encoding-stx2f in England to assess the risk to public health.

Methodology. One hundred and twelve

E. coli

(n=58 isolates encoded stx2f; n=54 isolates

E. coli

belonging to CC122 or CC722 that had eae but were negative for stx) isolated from patients' faecal specimens between 2015 and 2022 were genome sequenced and linked to epidemiological and clinical outcome data. All isolates were investigated for the presence of virulence genes and a maximum-likelihood phylogeny of isolates belonging to CC122 and CC722 was constructed.

Results. There were 52 cases infected with STEC harbouring stx2f between 2015 and 2022, with the majority identified in 2022. Most cases resided in the North of England (n=39/52, 75 %), were female (n=31, 59.6 %) and/or aged five and under (n=29, 55.8 %). Clinical outcome data were available for 40/52 cases (76.9 %) and 7/40(17.5 %) were diagnosed with STEC-HUS. In the two most common clonal complexes, CC122 and CC722, the presence of the stx2f-encoding prophage correlated with the presence of additional virulence genes, astA, bfpA and cdt, located on an 85kbp IncFIB plasmid.

Conclusions. Certain serotypes of

E. coli

harbouring stx2f cause severe clinical outcomes, including STEC-HUS. Public health advice and possible interventions are limited, as little is known about the animal and environmental reservoirs and transmission routes. We recommend more comprehensive and standardized collection of microbiological and epidemiological data, and routine sharing of sequencing data between public health agencies worldwide.
Temporal shifts in the predominant carbapenemase gene types among carbapenemase-producing Klebsiella pneumoniae isolated in Bangkok, Thailand, during 2013–2016
Authors: Sakamoto Noriko , Laolerd Warawut , Akeda Yukihiro , Sugawara Yo , Motooka Daisuke , Yamamoto Norihisa , Takeuchi Dan , Shanmugakani Rathina Kumar , Nishi Isao , Suzuki Masato , Shibayama Keigo , Iida Tetsuya , Santanirand Pitak , Tomono Kazunori , Hamada Shigeyuki
Published: June 2023

Introduction. Carbapenemase-producing Enterobacteriaceae (CPE) have emerged as a global threat to public health and clinical practice.

Hypothesis/Gap Statement. In Thailand, reports describing CPEs carrying bla
NDM and bla
OXA-48-like genes have been increasing recently; however, data on detailed plasmid analysis and temporal shift of sequence type and carbapenemase type are limited.

Aim. In this study, we analysed whole-genome sequencing (WGS) data of clinically isolated carbapenemase-producing

Klebsiella pneumoniae

(CPKP) to reveal the molecular epidemiology of CPKP in a tertiary-care hospital in Bangkok, Thailand.

Methodology. Seventy-seven non-duplicated CPKP isolates collected during 2013–2016 were examined for their drug-resistance genes, sequence types and phylogenetic relationships.

Results. All the tested isolates possessed carbapenemase gene(s), and the major type of carbapenemase gene in 2014–2015 was bla
NDM-1, whereas isolates in 2016 harboured more bla
OXA-232 than bla
NDM-1. Other carbapenemase gene variants, such as bla
NDM-4, bla
NDM-5, bla
OXA-48, bla
OXA-181 and bla
IMP-14 were detected in some CPKP isolates. Furthermore, this study revealed that CPKP co-harbouring two genes, bla
NDM-1 and bla
OXA-232 or bla
OXA-181, emerged during this period. Notably, such isolates co-carrying the two carbapenemase genes emerged in three different sequence types, even in a single hospital, and then spread clonally. The WGS of CPKP revealed a temporal shift of the predominant carbapenemase genes from bla
NDM-1 to bla
OXA-232 along with a variation in other carbapenemase gene types within a span of 4 years.

Conclusion. Our findings suggest that a substantial change in CPE types occurred in Thailand and potentially in Southeast Asian countries.
A comparative genome analysis of the Bacillota (Firmicutes) class Dehalobacteriia
Authors: Song Young C. , Holland Sophie I. , Lee Matthew , Chen Gao , Löffler Frank E. , Manefield Michael J. , Hugenholtz Philip , Kappler Ulrike
Published: June 2023

Dehalobacterium formicoaceticum is recognized for its ability to anaerobically ferment dichloromethane (DCM), and a catabolic model has recently been proposed. D. formicoaceticum is currently the only axenic representative of its class, the Dehalobacteriia, according to the Genome Taxonomy Database. However, substantial additional diversity has been revealed in this lineage through culture-independent exploration of anoxic habitats. Here we performed a comparative analysis of 10 members of the Dehalobacteriia, representing three orders, and infer that anaerobic DCM degradation appears to be a recently acquired trait only present in some members of the order Dehalobacteriales. Inferred traits common to the class include the use of amino acids as carbon and energy sources for growth, energy generation via a remarkable range of putative electron-bifurcating protein complexes and the presence of S-layers. The ability of D. formicoaceticum to grow on serine without DCM was experimentally confirmed and a high abundance of the electron-bifurcating protein complexes and S-layer proteins was noted when this organism was grown on DCM. We suggest that members of the Dehalobacteriia are low-abundance fermentative scavengers in anoxic habitats.
Evidence of horizontal gene transfer within porB in 19 018 whole-genome Neisseria spp. isolates: a global phylogenetic analysis
Authors: Manoharan-Basil Sheeba Santhini , Gestels Zina , Abdellati Saïd , Akomoneh Elvis Achondou , Kenyon Chris
Published: June 2023

The PorB porins are the major pore-forming proteins in the genus

Neisseria

. The trimeric PorB porins consist of 16 highly conserved transmembrane domains that form an amphipathic β-sheet connected by short periplasmic turns and eight extracellular hydrophilic loops. These loops are immunogenic and also play an important role in mediating antimicrobial influx. This study sought to (i) characterize the variations in Neisserial loop 3(355–438 bp) associated with intermediate resistance to penicillin/tetracycline and (ii) evaluate if there was evidence of horizontal gene transfer in any of the loops. We collated an integrated database consisting of 19 018

Neisseria

spp. genomes – 17 882

Neisseria gonorrhoeae

, 114

Neisseria meningitidis

and 1022 commensal

Neisseria

spp. To identify the porB alleles, a gene-by-gene approach (chewBBACA) was employed. To evaluate the presence of recombination events, the Recombination Detection Programme (RDP4) was used. In total, 3885 porB alleles were detected. Paralogues were identified in 17

Neisseria

isolates. Putative recombination was identified in loop regions. Intraspecies recombination among

N. gonorrhoeae

isolates and interspecies recombination between

N. meningitidis

and commensal

Neisseria

spp., and

N. gonorrhoeae

and

N. lactamica

were identified. Here, we present a large-scale study of 19 018

Neisseria

isolates to describe recombination and variation in the porB gene. Importantly, we found putative recombination in loop regions between the pathogenic and non-pathogenic

Neisseria

spp. These findings suggest the need for pheno- and genotypic surveillance of antimicrobial susceptibility in commensal

Neisseria

spp. to prevent the emergence of AMR in the pathogenic

Neisseria

. This article contains data hosted by Microreact.
Single-cell RNA sequencing reveals HIF1A as a severity-sensitive immunological scar in circulating monocytes of convalescent comorbidity-free COVID-19 patients
Authors: May Lilly , Chu Chang-Feng , Zielinski Christina E.
Published: June 2023

COVID-19, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is characterized by a wide range of clinical symptoms and a poorly predictable disease course. Although in-depth transcriptomic investigations of peripheral blood samples from COVID-19 patients have been performed, the detailed molecular mechanisms underlying an asymptomatic, mild or severe disease course, particularly in patients without relevant comorbidities, remain poorly understood. While previous studies have mainly focused on the cellular and molecular dissection of ongoing COVID-19, we set out to characterize transcriptomic immune cell dysregulation at the single-cell level at different time points in patients without comorbidities after disease resolution to identify signatures of different disease severities in convalescence. With single-cell RNA sequencing we reveal a role for hypoxia-inducible factor 1-alpha (HIF1A) as a severity-sensitive long-term immunological scar in circulating monocytes of convalescent COVID-19 patients. Additionally, circulating complexes formed by monocytes with either T cells or NK cells represent a characteristic cellular marker in convalescent COVID-19 patients irrespective of their preceding symptom severity. Together, these results provide cellular and molecular correlates of recovery from COVID-19 and could help in immune monitoring and in the design of new treatment strategies.
Anti-Viral and Anti-Inflammatory Therapeutic Effect of RAGE-Ig Protein Against Multiple SARS-CoV-2 Variants of Concern Demonstrated in K18-hACE2 Mouse and Syrian Golden Hamster Models
Authors: Dhanushkodi Nisha Rajeswari , Prakash Swayam , Quadiri Afshana , Zayou Latifa , Srivastava Ruchi , Shaik Amin Mohammed , Suzer Berfin , Ibraim Izabela Coimbra , Landucci Gary , Tifrea Delia F , Singer Mahmoud , Jamal Leila , Edwards Robert A , Vahed Hawa , Brown Lawrence , BenMohamed Lbachir
Published: June 2023

Significance

SARS-CoV-2 Variants of Concern (VOCs) continue to evolve and re-emerge with chronic inflammatory long-COVID sequelae necessitating the development of anti-inflammatory therapeutic molecules. Therapeutic effects of the Receptor for Advanced Glycation End products (RAGE) were reported in many inflammatory diseases. However, a therapeutic effect of the RAGE in COVID-19 has not been reported. In the present study, we investigated whether and how the RAGE-Ig fusion protein would have an anti-viral and anti-inflammatory therapeutic effect in the COVID-19 system.

Methods

The protective therapeutic effect of RAGE-Ig was determined in vitro in K18-hACE2 transgenic mice and Syrian golden hamsters infected with six various VOCs of SARS-CoV-2. The underlying anti-viral mechanism of RAGE-Ig was determinedin vitroin SARS-CoV-2-infected human lung epithelial cells (BEAS-2B).

Results

Following treatment of K18-hACE2 mice and hamsters infected with various SARS-CoV-2 VOCs with RAGE-Ig, we demonstrated: (i) significant dose-dependent protection (i.e. greater survival, less weight loss, lower virus replication in the lungs); (ii) a reduction of inflammatory macrophages (F4/80+/Ly6C+) and neutrophils (CD11b+/Ly6G+) infiltrating the infected lungs; (iii) a RAGE-Ig dose-dependent increase in the expression of type I interferons (IFN-α, and IFN-β) and type III interferon (IFNλ2) and a decrease in the inflammatory cytokines (IL-6 and IL-8) in SARS-CoV-2-infected human lung epithelial cells; and (iv) a dose-dependent decrease in the expression of CD64 (FcgR1) on monocytes and lung epithelial cells from symptomatic COVID-19 patients.

Conclusion

Our pre-clinical findings revealed type I and III interferons-mediated anti-viral and anti-inflammatory therapeutic effects of RAGE-Ig protein against COVID-19 caused by multiple SARS-CoV-2 VOCs.
An evolutionarily conserved strategy for ribosome binding and inhibition by β-coronavirus non-structural protein 1
Authors: Maurina Stephanie F. , O’Sullivan John P. , Sharma Geetika , Pineda Rodriguez Daniel C. , MacFadden Andrea , Cendali Francesca , Henen Morkos A. , Kieft Jeffrey S. , Glasgow Anum , Steckelberg Anna-Lena
Published: June 2023

An important pathogenicity factor of SARS-CoV-2 and related coronaviruses is Nsp1, which suppresses host gene expression and stunts antiviral signaling. SARS-CoV-2 Nsp1 binds the ribosome to inhibit translation through mRNA displacement and induces degradation of host mRNAs through an unknown mechanism. Here we show that Nsp1-dependent host shutoff is conserved in diverse coronaviruses, but only Nsp1 from β-CoV inhibits translation through ribosome binding. The C-terminal domain of all β-CoV Nsp1s confers high-affinity ribosome-binding despite low sequence conservation. Modeling of interactions of four Nsp1s to the ribosome identified few absolutely conserved amino acids that, together with an overall conservation in surface charge, form the β-CoV Nsp1 ribosome-binding domain. Contrary to previous models, the Nsp1 ribosome-binding domain is an inefficient translation inhibitor. Instead, the Nsp1-CTD likely functions by recruiting Nsp1’s N-terminal “effector” domain. Finally, we show that a viralcis-acting RNA element has co-evolved to fine-tune SARS-CoV-2 Nsp1 function, but does not provide similar protection against Nsp1 from related viruses. Together, our work provides new insight into the diversity and conservation of ribosome-dependent host-shutoff functions of Nsp1, knowledge that could aide future efforts in pharmacological targeting of Nsp1 from SARS-CoV-2, but also related human-pathogenic β-coronaviruses. Our study also exemplifies how comparing highly divergent Nsp1 variants can help to dissect the different modalities of this multi-functional viral protein.
Experimental study of the operating parameters on the performance of a single-stage Stirling cryocooler cooling infrared sensor for space application
Authors: Kharadi Fayaz , A Karthikeyan , Bhojwani Virendra , Dixit Prachi , Kanu Nand Jee , Jain Nidhi
Published: June 2023

Purpose

The purpose of this study is to achieve lower and lower temperature as infrared sensors works faster and better used for space application. For getting good quality images from space, the infrared sensors are need to keep in cryogenic temperature. Cooling to cryogenic temperatures is necessary for space-borne sensors used for space applications. Infrared sensors work faster or better at lower temperatures. It is the need for time to achieve lower and lower temperatures.

Design/methodology/approach

This study presents the investigation of the critical Stirling cryocooler parameters that influence the cold end temperature. In the paper, the design approach, the dimensions gained through thermal analysis, experimental procedure and testing results are discussed.

Findings

The effect of parameters such as multilayer insulation, helium gas charging pressure, compressor input voltage and cooling load was investigated. The performance of gold-plated and aluminized multilayer insulation is checked. The tests were done with multilayer insulation covering inside and outside the Perspex cover.

Practical implications

By using aluminized multilayer insulation inside and outside the Perspex cover, the improvement of 16 K in cool-down temperature was achieved. The cryocooler is charged with helium gas. The pressure varies between 14 and 18 bar. The optimum cooling is obtained for 17 bar gas pressure. The piston stroke increased as the compressor voltage increased, resulting in total helium gas compression. The optimum cool-down temperature was attained at 85 V.

Originality/value

The cryocooler is designed to achieve the cool-down temperature of 2 W cooling load at 100 K. The lowest cool-down temperature recorded was 105 K at a 2 W cooling load. Multilayer insulation is the major item that keeps the thermal radiation from the sun from reaching the copper tip.