bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimization of fermentation conditions for surfactin production by B. subtilis YPS-32
Authors: Zhou Yingjun , Yang Xiaoxue , Li Qing , Peng Zheng , Li Jianghua , Zhang Juan
Published: April 2023

Background

Surfactin produced by microbial fermentation has attracted increasing attention because of its low toxicity and excellent antibacterial activity. However, its application is greatly limited by high production costs and low yield. Therefore, it is important to produce surfactin efficiently while reducing the cost. In this study, B. subtilis strain YPS-32 was used as a fermentative strain for the production of surfactin, and the medium and culture conditions for the fermentation of B. subtilis YPS-32 for surfactin production were optimized.

Results

First, Landy 1 medium was screened as the basal medium for surfactin production by B. subtilis strain YPS-32. Then, using single-factor optimization, the optimal carbon source for surfactin production by B. subtilis YPS-32 strain was determined to be molasses, nitrogen sources were glutamic acid and soybean meal, and inorganic salts were KCl, K2HPO4, MgSO4, and Fe2(SO4)3. Subsequently, using Plackett-Burman design, MgSO4, time (h) and temperature (°C) were identified as the main effect factors. Finally, Box-Behnken design were performed on the main effect factors to obtain optimal fermentation conditions: temperature of 42.9 °C, time of 42.8 h, MgSO4 = 0.4 g·L− 1. This modified Landy medium was predicted to be an optimal fermentation medium: molasses 20 g·L− 1, glutamic acid 15 g·L− 1, soybean meal 4.5 g·L− 1, KCl 0.375 g·L− 1, K2HPO4 0.5 g·L− 1, Fe2(SO4)3 1.725 mg·L− 1, MgSO4 0.4 g·L− 1. Using the modified Landy medium, the yield of surfactin reached 1.82 g·L− 1 at pH 5.0, 42.9 ℃, and 2% inoculum for 42.8 h, which was 2.27-fold higher than that of the Landy 1 medium in shake flask fermentation. Additionally, under these optimal process conditions, further fermentation was carried out at the 5 L fermenter level by foam reflux method, and at 42.8 h of fermentation, surfactin reached a maximum yield of 2.39 g·L− 1, which was 2.96-fold higher than that of the Landy 1 medium in 5 L fermenter.

Conclusion

In this study, the fermentation process of surfactin production by B. subtilis YPS-32 was improved by using a combination of single-factor tests and response surface methodology for test optimization, which laid the foundation for its industrial development and application.
Epidemiology of clinically isolated methicillin-resistant Staphylococcus aureus (MRSA) and its susceptibility to linezolid and vancomycin in Egypt: a systematic review with meta-analysis
Authors: Azzam Ahmed , Khaled Heba , Mosa Maha , Refaey Neveen , AlSaifi Mohammed , Elsisi Sarah , Elagezy Fatma Khaled , Mohsen May
Published: April 2023

Background

Methicillin-resistantStaphylococcus aureus(MRSA) is a major nosocomial pathogen that causes severe morbidity and mortality worldwide. For the establishment of national strategies to combat MRSA infection in each country, accurate and current statistics characterizing the epidemiology of MRSA are essential. The purpose of this study was to determine the prevalence of MRSA amongStaphylococcus aureusclinical isolates in Egypt. In addition, we aimed to compare different diagnostic methods for MRSA and determine the pooled resistance rate of linezolid and vancomycin to MRSA. To address this knowledge gap, we conducted a systematic review with meta-analysis.

Methods

A comprehensive literature search from inception to October 2022 of the following databases was performed: MEDLINE [PubMed], Scopus, Google Scholar, and Web of Science. The review was conducted following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) Statement. Based on the random effects model, results were reported as proportions with a 95% confidence interval (CI). Analyses of the subgroups were conducted. A sensitivity analysis was conducted to test the robustness of the results.

Results

A total of sixty-four (64) studies were included in the present meta-analysis, with a total sample size of 7171 subjects. The overall prevalence of MRSA was 63% [95% CI: 55–70]. Fifteen (15) studies used both PCR and cefoxitin disc diffusion for MRSA detection, with a pooled prevalence rate of 67% [95% CI: 54–79] and 67% [95% CI: 55–80], respectively. While nine (9) studies used both PCR and Oxacillin disc diffusion for MRSA detection, the pooled prevalences were 60% [95% CI: 45–75] and 64% [95% CI: 43–84], respectively. Furthermore, MRSA appeared to be less resistant to linezolid than vancomycin, with a pooled resistance rate of 5% [95% CI: 2–8] to linezolid and 9% [95% CI: 6–12] to vancomycin, respectively.

Conclusion

Our review highlights Egypt's high MRSA prevalence. The cefoxitin disc diffusion test results were found to be consistent with PCR identification of themecAgene. A prohibition on antibiotic self-medication and efforts to educate healthcare workers and patients about the proper use of antimicrobials may be required to prevent further increases.
Diagnostic value of neutrophil gelatinase-associated lipocalin (NGAL) as an early biomarker for detection of renal failure in hypertensives: a case–control study in a regional hospital in Ghana
Authors: Danquah Mark , Owiredu William K. B. A. , Jnr B. A. Eghan , Serwaa Dorcas , Odame Anto Enoch , Peprah Maxwell Owusu , Obirikorang Christian , Fondjo Linda A.
Published: April 2023

Background

Renal failure is one of the most serious vascular effects of hypertension. For better therapy and prevention of complications, early kidney disease identification in these patients is absolutely essential. However, current studies have proposed plasma Neutrophil Gelatinase Associated Lipocalin (pNGAL) to be a better biomarker comparative to serum creatinine (SCr). This study assessed the diagnostic utility of plasma neutrophil gelatinase-associated lipocalin (pNGAL) as a biomarker for early nephropathy diagnosis in hypertensive individuals.

Methods

This hospital-based case–control study comprised 140 hypertensives and 70 healthy participants. A well-structured questionnaire and patient case notes were used to document relevant demographic and clinical information. 5 ml of venous blood sample was taken to measure fasting blood sugar levels, creatinine, and plasma NGAL levels. All data were analyzed using the Statistical Package for Social Sciences (SPSS release 20.0, copyrite©SPSS Inc.) and ap-value < 0.05 was considered statistically significant.

Results

In this study the plasma neutrophil gelatinase-associated lipocalin (NGAL) levels were significantly higher in cases compared to controls. Hypertensive cases also had significantly higher waist-circumference compared to the control group. The median fasting blood sugar level was significantly higher in cases compared to controls. This study established the use of Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), and Cockcroft and Gault formula (CG) as the most accurate predictive equations for assessing renal dysfunction. The threshold for NGAL above which renal impairment can be assessed was found to be 109.4 ng/ml (sen-91%, spec. – 68%), 120 ng/ml (sen- 100%, spec- 72%) and 118.6 ng/ml (sen- 83%, spec- 72%) for MDRD, CKD-EPI and CG equations respectively. The prevalence of CKD was 16.4%, 13.6% and 20.7% respectively using the MDRD, CKD-EPI and CG.

Conclusion

From this study, pNGAL is a better indicator of kidney impairment in the early stages of CKD as compared with sCr in general hypertensive population.
Use of pregnancy personalised follow-up in case of maternal social vulnerability to reduce prematurity and neonatal morbidity
Authors: Crequit Simon , Bierry Gregory , Maria Perbellini , Bouali Sakina , La Tour Adelaïde Dupre , Sgihouar Naima , Renevier Bruno
Published: April 2023

Background

Social deprivation is a major risk factor of adverse pregnancy outcomes. Yet, there is few studies evaluating interventions aiming at reducing the impact of social vulnerability on pregnancy outcomes.

Objective

To compare pregnancy outcomes between patients that received personalized pregnancy follow-up (PPFU) to address social vulnerability versus standard care.

Methods

Retrospective comparative cohort in a single institution between 2020 and 2021. A total of 3958 women with social vulnerability that delivered a singleton after 14 gestational weeks were included, within which 686 patients had a PPFU. Social vulnerability was defined by the presence of at least one of the following characteristics: social isolation, poor or insecure housing conditions, no work-related household income, and absence of standard health insurance (these four variables were combined as a social deprivation index (SDI)), recent immigration (< 12 month), interpersonal violence during pregnancy, being handicaped or minor, addiction during pregnancy. Maternal characteristics and pregnancy outcomes were compared between patients that received PPFU versus standard care. The associations between poor pregnancy outcomes (premature birth before 37 gestational weeks (GW), premature birth before 34 GW, small for gestational age (SGA) and PPFU were tested using multivariate logistic regression and propensity score matching.

Results

After adjustment on SDI, maternal age, parity, body mass index, maternal origin and both high medical and obstetrical risk level before pregnancy, PPFU was an independent protective factor of premature birth before 37 gestational weeks (GW) (aOR = 0.63, 95%CI[0.46–0.86]). The result was similar for premature birth before 34 GW (aOR = 0.53, 95%CI [0.34–0.79]). There was no association between PPFU and SGA (aOR = 1.06, 95%CI [0.86 – 1.30]). Propensity score adjusted (PSa) OR for PPFU using the same variables unveiled similar results, PSaOR = 0.63, 95%CI[0.46–0.86] for premature birth before 37 GW, PSaOR = 0.52, 95%CI [0.34–0.78] for premature birth before 34 GW and PSaOR = 1.07, 95%CI [0.86 – 1.33] for SGA.

Conclusions

This work suggests that PPFU improves pregnancy outcomes and emphasizes that the detection of social vulnerability during pregnancy is a major health issue.
Impact of maternal body mass index on outcomes of singleton pregnancies after assisted reproductive technology: a 14-year analysis of the US Nationwide Inpatient Sample
Authors: Li Yi-Ping , Li Wei-Jiun , Hsieh Wen-Chi , Chen Li-Shan , Yu Cheng-Wei
Published: April 2023

Background

Obesity is increasing globally, which affects multiple human functions, including reproductive health. Many women with overweight and obesity of child-bearing years are treated with assisted reproductive technology (ART). However, the clinical impact of body mass index (BMI) on pregnancy outcomes after ART remains to be determined. Therefore, this population-based retrospective cohort study aimed to assess whether and how higher BMI affects singleton pregnancy outcomes.

Methods

This study used the large nationally representative database of the US National Inpatient Sample (NIS), extracting data of women with singleton pregnancies who had received ART from 2005 to 2018. Diagnostic codes of the International Classification of Diseases, Ninth and Tenth edition (ICD-9 and ICD-10) were used to identify females admitted to US hospitals with delivery-related discharge diagnoses or procedures and secondary diagnostic codes for ART, including in vitro fertilization. The included women were further categorized into three groups based on BMI values < 30, 30–39, and ≥ 40 kg/m2. Univariate and multivariable regression analysis were conducted to assess the associations between study variables and maternal and fetal outcomes.

Results

Data of totally 17,048 women were included in the analysis, which represented a population of 84,851 women in the US. Number of women in the three BMI groups were 15, 878 (BMI < 30 kg/m2), 653 (BMI 30–39 kg/m2), and 517 (BMI ≥ 40 kg/m2), respectively. The multivariable regression analysis revealed that, compared to BMI < 30 kg/m2, BMI 30–39 kg/m2 was significantly associated with increased odds for pre-eclampsia and eclampsia (adjusted OR = 1.76, 95% CI = 1.35, 2.29), gestational diabetes (adjusted OR = 2.25, 95% CI = 1.70, 2.98), and Cesarean delivery (adjusted OR = 1.36, 95% CI = 1.15, 1.60). Further, BMI ≥ 40 kg/m2 was associated with greater odds for pre-eclampsia and eclampsia (adjusted OR = 2.25, 95% CI = 1.73, 2.94), gestational diabetes (adjusted OR = 3.64, 95% CI = 2.80, 4.72), disseminated intravascular coagulation (DIC) (adjusted OR = 3.79, 95% CI = 1.47, 9.78), Cesarean delivery (adjusted OR = 1.85, 95% CI = 1.54, 2.23), and hospital stay ≥ 6 days (adjusted OR = 1.60, 95% CI = 1.19, 2.14). However, higher BMI was not significantly associated with greater risk of the fetal outcomes assessed.

Conclusions

Among US pregnant women who received ART, having a higher BMI level independently increases the risk for adverse maternal outcomes such as pre-eclampsia and eclampsia, gestational diabetes, DIC, longer hospital stays, and higher rates of Cesarean delivery, while risk is not increased for fetal outcomes.
Impact of pharmacogenomic DPYD variant guided dosing on toxicity in patients receiving fluoropyrimidines for gastrointestinal cancers in a high-volume tertiary centre
Authors: Lau David K. , Fong Caroline , Arouri Faten , Cortez Lillian , Katifi Hannah , Gonzalez-Exposito Reyes , Razzaq Muhammad Bilal , Li Su , Macklin-Doherty Aislinn , Hernandez Monica Arenas , Hubank Michael , Fribbens Charlotte , Watkins David , Rao Sheela , Chau Ian , Cunningham David , Starling Naureen
Published: April 2023

Background

Dihydropyrimidine dehydrogenase (DPD) is a key enzyme in the metabolism of fluoropyrimidines. Variations in the encodingDPYDgene are associated with severe fluoropyrimidine toxicity and up-front dose reductions are recommended. We conducted a retrospective study to evaluate the impact of implementingDPYDvariant testing for patients with gastrointestinal cancers in routine clinical practice in a high volume cancer centre in London, United Kingdom.

Methods

Patients receiving fluoropyrimidine chemotherapy for gastrointestinal cancer prior to, and following the implementation ofDPYDtesting were identified retrospectively. After November 2018, patients were tested forDPYDvariants c.1905+1G>A (DPYD*2A), c.2846A>T (DPYDrs67376798), c.1679T>G (DPYD*13), c.1236G>A (DPYDrs56038477), c.1601G>A (DPYD*4) prior to commencing fluoropyrimidines alone or in combination with other cytotoxics and/or radiotherapy. Patients with aDPYDheterozygous variant received an initial dose reduction of 25–50%. Toxicity by CTCAE v4.03 criteria was compared betweenDPYDheterozygous variant and wild type carriers.

Results

Between 1stDecember 2018 and 31stJuly 2019, 370 patients who were fluoropyrimidine naïve underwent aDPYDgenotyping test prior to receiving a capecitabine (n = 236, 63.8%) or 5FU (n = 134, 36.2%) containing chemotherapy regimen. 33 patients (8.8%) were heterozygousDPYDvariant carriers and 337 (91.2%) were wild type. The most prevalent variants were c.1601G > A (n = 16) and c.1236G > A (n = 9). Mean relative dose intensity for the first dose was 54.2% (range 37.5–75%) forDPYDheterozygous carriers and 93.2% (42.9–100%) forDPYDwild type carriers. Overall grade 3 or worse toxicity was similar inDPYDvariant carriers (4/33, 12.1%) as compared to wild-type carriers (89/337, 25.7%;P = 0.0924).

Conclusions

Our study demonstrates successful routineDPYDmutation testing prior to the initiation of fluoropyrimidine chemotherapy with high uptake. In patients withDPYDheterozygous variants with pre-emptive dose reductions, high incidence of severe toxicity was not observed. Our data supports routineDPYDgenotype testing prior to commencement of fluoropyrimidine chemotherapy.
Technical failure rates for biometry between swept-source and older-generation optical coherence methods: a review and meta-analysis
Authors: Kanclerz Piotr , Hecht Idan , Tuuminen Raimo
Published: April 2023

Purpose

Precise ocular measurements are fundamental for achieving excellent target refraction following both cataract surgery and refractive lens exchange. Biometry devices with swept-source optical coherence tomography (SS-OCT) employ longer wavelengths (1055–1300 nm) in order to have better penetration through opaque lenses than those with partial coherence interferometry (PCI) or low-coherence optical reflectometry (LCOR) methods. However, to date a pooled analysis showing the technical failure rate (TFR) between the methods has not been published. The aim of this study was to compare the TFR in SS-OCT and in PCI/LCOR biometry.

Methods

PubMed and Scopus were used to search the medical literature as of Feb 1, 2022. The following keywords were used in various combinations: optical biometry, partial coherence interferometry, low-coherence optical reflectometry, swept-source optical coherence tomography. Only clinical studies referring to patients undergoing routine cataract surgery, and employing at least two (PCI or LCOR vs. SS-OCT) optical methods for optical biometry in the same cohort of patients were included.

Results

Fourteen studies were included in the final analysis, which presented results of 2,459 eyes of at least 1,853 patients. The overall TFR of all included studies was 5.47% (95% confidence interval [CI]: 3.66–8.08%; overall I2 = 91.49%). The TFR was significantly different among the three methods (p < 0.001): 15.72% for PCI (95% CI: 10.73–22.46%; I2 = 99.62%), 6.88% for LCOR (95% CI: 3.26–13.92%; I2 = 86.44%), and 1.51% for SS-OCT (95% CI: 0.94–2.41%; I2 = 24.64%). The pooled TFR for infrared methods (PCI and LCOR) was 11.12% (95% CI: 8.45–14.52%; I2 = 78.28%), and was also significantly different to that of SS-OCT: 1.51% (95% CI: 0.94–2.41%; I2 = 24.64%; p < 0.001).

Conclusions

A meta-analysis of the TFR of different biometry methods highlighted that SS-OCT biometry resulted in significantly decreased TFR compared to PCI/LCOR devices.
Dry needling in a multimodal rehabilitation protocol following rotator cuff repair surgery: study protocol for a double-blinded randomized sham-controlled trial
Authors: Naseri Faeze , Dadgoo Mehdi , Pourahmadi Mohammadreza , Amroodi Morteza Nakhaei , Azizi Shirin , Tabrizian Pouria , Amiri Ali
Published: April 2023

Background

Rotator cuff tear (RCT) is one of the main causes of shoulder pain and dysfunction. Rotator cuff repair (RCR) is a common surgical procedure for the management of RCTs. Presence of myofascial trigger points (MTrP) as a result of surgical procedure can aggravate postoperative shoulder pain. The purpose of this protocol is to describe a randomized controlled trial design to evaluate the effect of implementing 4 sessions of myofascial trigger point dry needling (MTrP-DN) within a multimodal rehabilitation protocol following RCR surgery.

Methods

Forty-six participants aged 40–75 will be recruited having postoperative shoulder pain after RCR and meeting the inclusion criteria. Participants will be randomly divided into 2 groups: One group will undergo MTrP-DN, manual therapy, exercise therapy and electrotherapy and the other will receive sham dry needling (S-DN), manual therapy, exercise therapy and electrotherapy. This protocol will cover 4 weeks of intervention. The primary outcome measure will be the Numeric Pain Rating Scale (NPRS) for pain. Secondary outcome measures will be Shoulder Pain and Disability Index (SPDI), range of motion (ROM), strength and adverse events.

Discussion

This is the first study to investigate the use of 4 sessions of MTrP-DN in combination with a multimodal rehabilitation protocol for postoperative shoulder pain, restriction, weakness and dysfunction following RCR. The results of this study may help to determine the effect of MTrP-DN on various outcomes after RCR surgery.

Trial registration

This trial was registered at the (https://www.irct.ir), (IRCT20211005052677N1) on 19/2/2022.
TRPM4 regulates hilar mossy cell loss in temporal lobe epilepsy
Authors: Mundrucz Laura , Kecskés Angéla , Henn-Mike Nóra , Kóbor Péter , Buzás Péter , Vennekens Rudi , Kecskés Miklós
Published: April 2023

Background

Mossy cells comprise a large fraction of excitatory neurons in the hippocampal dentate gyrus, and their loss is one of the major hallmarks of temporal lobe epilepsy (TLE). The vulnerability of mossy cells in TLE is well known in animal models as well as in patients; however, the mechanisms leading to cellular death is unclear.

Results

Transient receptor potential melastatin 4 (TRPM4) is a Ca2+-activated non-selective cation channel regulating diverse physiological functions of excitable cells. Here, we identified that TRPM4 is present in hilar mossy cells and regulates their intrinsic electrophysiological properties including spontaneous activity and action potential dynamics. Furthermore, we showed that TRPM4 contributes to mossy cells death following status epilepticus and therefore modulates seizure susceptibility and epilepsy-related memory deficits.

Conclusions

Our results provide evidence for the role of TRPM4 in MC excitability both in physiological and pathological conditions.
Genetic evidence implicating natriuretic peptide receptor-3 in cardiovascular disease risk: a Mendelian randomization study
Authors: Cronjé Héléne T. , Karhunen Ville , Hovingh G. Kees , Coppieters Ken , Lagerstedt Jens O. , Nyberg Michael , Gill Dipender
Published: April 2023

Background

C-type natriuretic peptide (CNP) is a known target for promoting growth and has been implicated as a therapeutic opportunity for the prevention and treatment of cardiovascular disease (CVD). This study aimed to explore the effect of CNP on CVD risk using the Mendelian randomization (MR) framework.

Methods

Instrumental variables mimicking the effects of pharmacological intervention on CNP were identified as uncorrelated genetic variants located in the genes coding for its primary receptors, natriuretic peptide receptors-2 and 3 (NPR2 and NPR3), that associated with height. We performed MR and colocalization analyses to investigate the effects of NPR2 signalling and NPR3 function on CVD outcomes and risk factors. MR estimates were compared to those obtained when considering height variants from throughout the genome.

Results

Genetically-proxied reduced NPR3 function was associated with a lower risk of CVD, with odds ratio (OR) 0.74 per standard deviation (SD) higher NPR3-predicted height, and 95% confidence interval (95% CI) 0.64–0.86. This effect was greater in magnitude than observed when considering height variants from throughout the genome. For CVD subtypes, similar MR associations for NPR3-predicted height were observed when considering the outcomes of coronary artery disease (0.75, 95% CI 0.60–0.92), stroke (0.69, 95% CI 0.50–0.95) and heart failure (0.77, 95% CI 0.58–1.02). Consideration of CVD risk factors identified systolic blood pressure (SBP) as a potential mediator of the NPR3-related CVD risk lowering. For stroke, we found that the MR estimate for NPR3 was greater in magnitude than could be explained by a genetically predicted SBP effect alone. Colocalization results largely supported the MR findings, with no evidence of results being driven by effects due to variants in linkage disequilibrium. There was no MR evidence supporting effects of NPR2 on CVD risk, although this null finding could be attributable to fewer genetic variants being identified to instrument this target.

Conclusions

This genetic analysis supports the cardioprotective effects of pharmacologically inhibiting NPR3 receptor function, which is only partly mediated by an effect on blood pressure. There was unlikely sufficient statistical power to investigate the cardioprotective effects of NPR2 signalling.
Electrochemical aptasensor based on the engineered core-shell MOF nanostructures for the detection of tumor antigens
Authors: Khan Suliman , Cho William C. , Sepahvand Afrooz , Haji Hosseinali Sara , Hussain Arif , Nejadi Babadaei Mohammad Mahdi , Sharifi Majid , Falahati Mojtaba , Jaragh-Alhadad Laila Abdulmohsen , ten Hagen Timo L. M. , Li Xin
Published: April 2023

It is essential to develop ultrasensitive biosensors for cancer detection and treatment monitoring. In the development of sensing platforms, metal-organic frameworks (MOFs) have received considerable attention as potential porous crystalline nanostructures. Core-shell MOF nanoparticles (NPs) have shown different diversities, complexities, and biological functionalities, as well as significant electrochemical (EC) properties and potential bio-affinity to aptamers. As a result, the developed core-shell MOF-based aptasensors serve as highly sensitive platforms for sensing cancer biomarkers with an extremely low limit of detection (LOD). This paper aimed to provide an overview of different strategies for improving selectivity, sensitivity, and signal strength of MOF nanostructures. Then, aptamers and aptamers-modified core-shell MOFs were reviewed to address their functionalization and application in biosensing platforms. Additionally, the application of core-shell MOF-assisted EC aptasensors for detection of several tumor antigens such as prostate-specific antigen (PSA), carbohydrate antigen 15-3 (CA15-3), carcinoembryonic antigen (CEA), human epidermal growth factor receptor-2 (HER2), cancer antigen 125 (CA-125), cytokeratin 19 fragment (CYFRA21-1), and other tumor markers were discussed. In conclusion, the present article reviews the advancement of potential biosensing platforms toward the detection of specific cancer biomarkers through the development of core-shell MOFs-based EC aptasensors.
“The familiar taste of poison”: a qualitative study of multi-level motivations for stimulant use in sexual minority men living in South Florida
Authors: Davis-Ewart Leah , Lee Ji-Young , Viamonte Michael , Colon-Burgos Josè , Harkness Audrey , Kanamori Mariano , Duncan Dustin T. , Doblecki-Lewis Susanne , Carrico Adam W. , Grov Christian
Published: April 2023

Background

In the US, stimulant use is associated with a 3–6 times greater rate of HIV seroconversion in sexual minority men (SMM) than in those who do not use stimulants. Annually, 1 in 3 SMM who HIV seroconvert will be persistent methamphetamine (meth) users. The primary objective of this qualitative study was to explore experiences of stimulant use in SMM living in South Florida, a high priority region for the Ending the HIV Epidemic initiative.

Methods

The sample included 25 SMM who use stimulants, recruited via targeted ads on social networking apps. Participants completed one-on-one semi-structured qualitative interviews, conducted from July 2019 through February 2020. A general inductive approach was used to identify themes relating to experiences, motivations, and overall relationship with stimulant use.

Results

Mean age of participants was 38.8, ranging from 20 to 61 years old. Participants were 44% White, 36% Latino, 16% Black and 4% Asian. Most participants were born in the US, self-identified as gay, and preferred meth as their stimulant of choice. Themes included: (1) stimulants as cognitive enhancements for focus or task completion, including transitioning to meth after first using prescription psychostimulants; (2) unique South Florida environment where participants could be open regarding their sexual minority status while also being influential on their stimulant use; (3) stimulant use as both stigmatizing and a coping mechanism for stigma. Participants anticipated stigma by family and potential sexual partners due to their stimulant use. They also reported using stimulants to cope with feelings of stigma due to their minoritized identities.

Conclusion

This study is among the first to characterize motivations for stimulant use in SMM living in South Florida. Results highlight both the risk and protective factors of the South Florida environment, psychostimulant misuse as a risk for meth initiation, and the role of anticipated stigma on stimulant use in SMM. Understanding stimulant use motivations can help to shape intervention development. This includes developing interventions that address individual, interpersonal, and cultural factors that drive stimulant use and increase risk of HIV acquisition.

Trial registration NCT04205487.
Association of oily fish and nonoily fish intakes with all-cause mortality and cause-specific mortality: a large population-based prospective study
Authors: Zhou Jian , Tan Xiankui , Li Yihan , Wan Rongjun , Wu Ziyi , Lin Zhengjun , Wang Wanchun , Luo Yingquan , Liu Tang
Published: April 2023

Background

There are inconsistent results of cohort studies analyzing the association between fish intake and mortality.

Objective

This study was performed to explore the association of oily fish consumption and nonoily fish consumption with all-cause mortality and cause-specific mortality.

Methods

A total of 431,062 participants from the UK Biobank who were without cancer or cardiovascular disease (CVD) at baseline between 2006 and 2010 were included in this study, and they were followed up through 2021. We constructed Cox proportional hazard models to calculate the hazard ratio (HR) and 95% confidence interval (CI) to assess the correlation of oily fish and nonoily fish intakes with mortality. Then, we performed subgroup analyses, and sensitivity analyses were developed and performed to examine the robustness of this study.

Results

Among the participants, 383,248 (88.9%) and 410,499 (95.2%) consumed oily fish and nonoily fish, respectively. Compared with the participants who did not consume oily fish, the adjusted HRs for the association of oily fish consumption (1 serving/week) with all-cause mortality and CVD mortality were 0.93 (0.87 to 0.98; p < 0.05) and 0.85 (0.74 to 0.98; p < 0.05), respectively. The multivariable-adjusted HRs of all-cause mortality for those who reported consuming < 1 serving/week of oily fish were 0.92 (0.86 to 0.98; p < 0.05).

Conclusion

Compared with participants who reported never consuming oily fish, the consumption of oily fish with 1 serving/week was more beneficial for all-cause and CVD mortality.
STIL/AURKA axis promotes cell proliferation by influencing primary cilia formation in bladder cancer
Authors: Li Jingxian , Qi Yuanjiong , Li Bo , Liu Yan , Yang Kuo , Zhang Zhihong , Zhu Jianqiang , Du E.
Published: April 2023

Background

The primary cilia (PC) is a microtubule-based and nonmotile organelle which protrudes from the surface of almost all mammalian cells. At present, PC has been found to be a deficiency or loss in multiple cancers. Restoring PC could be a novel targeting therapy strategy. Our research showed that PC was reduced in human bladder cancer (BLCA) cells, and PC deficiency promotes cell proliferation. However, the concrete mechanisms remain unknown. SCL/TAL1 interrupting locus (STIL), a PC-related protein, was screened in our previous study and could influence the cell cycle by regulating PC in tumor cells. In this study, we aimed to elucidate the function of STIL for PC to explore the underlying mechanism of PC in BLCA.

Methods

Public database analysis, western blot, and enzyme-linked immunosorbent assay (ELISA) were used to screen genes and explore gene expression alteration. Immunofluorescence and western blot were utilized to investigate PC. Wound healing assay, clone formation assay, and CCK-8 assay were used to explore cell migration, growth, and proliferation. The co-immunoprecipitation and western blot were employed to reveal the interaction of STIL and AURKA.

Results

We found that high STIL expression is correlated with poor outcomes of BLCA patients. Further analysis revealed that STIL overexpression could inhibit PC formation, activate SHH signaling pathways, and promote cell proliferation. In contrast, STIL-knockdown could promote PC formation, inactivate SHH signaling, and inhibit cell proliferation. Furthermore, we found that the regulatory functions of STIL for PC depend on AURKA. STIL could influence proteasome activity and maintain AURKA stabilization. AURKA-knockdown could reverse PC deficiency caused by STIL overexpression for PC in BLCA cells. We observed that co-knockdown in STIL and AURKA significantly enhanced PC assembly.

Conclusion

In summary, our result provides a potential therapy target for BLCA based on the restoration of PC.
A tumor focused approach to resolving the etiology of DNA mismatch repair deficient tumors classified as suspected Lynch syndrome
Authors: Walker Romy , Mahmood Khalid , Joo Jihoon E. , Clendenning Mark , Georgeson Peter , Como Julia , Joseland Sharelle , Preston Susan G. , Antill Yoland , Austin Rachel , Boussioutas Alex , Bowman Michelle , Burke Jo , Campbell Ainsley , Daneshvar Simin , Edwards Emma , Gleeson Margaret , Goodwin Annabel , Harris Marion T. , Henderson Alex , Higgins Megan , Hopper John L. , Hutchinson Ryan A. , Ip Emilia , Isbister Joanne , Kasem Kais , Marfan Helen , Milnes Di , Ng Annabelle , Nichols Cassandra , O’Connell Shona , Pachter Nicholas , Pope Bernard J. , Poplawski Nicola , Ragunathan Abiramy , Smyth Courtney , Spigelman Allan , Storey Kirsty , Susman Rachel , Taylor Jessica A. , Warwick Linda , Wilding Mathilda , Williams Rachel , Win Aung K. , Walsh Michael D. , Macrae Finlay A. , Jenkins Mark A. , Rosty Christophe , Winship Ingrid M. , Buchanan Daniel D. ,   for the Family Cancer Clinics of Australia
Published: April 2023

Routine screening of tumors for DNA mismatch repair (MMR) deficiency (dMMR) in colorectal (CRC), endometrial (EC) and sebaceous skin (SST) tumors leads to a significant proportion of unresolved cases classified as suspected Lynch syndrome (SLS). SLS cases (n = 135) were recruited from Family Cancer Clinics across Australia and New Zealand. Targeted panel sequencing was performed on tumor (n = 137; 80×CRCs, 33×ECs and 24xSSTs) and matched blood-derived DNA to assess for microsatellite instability status, tumor mutation burden, COSMIC tumor mutational signatures and to identify germline and somatic MMR gene variants. MMR immunohistochemistry (IHC) and MLH1 promoter methylation were repeated. In total, 86.9% of the 137 SLS tumors could be resolved into established subtypes. For 22.6% of these resolved SLS cases, primary MLH1 epimutations (2.2%) as well as previously undetected germline MMR pathogenic variants (1.5%), tumor MLH1 methylation (13.1%) or false positive dMMR IHC (5.8%) results were identified. Double somatic MMR gene mutations were the major cause of dMMR identified across each tumor type (73.9% of resolved cases, 64.2% overall, 70% of CRC, 45.5% of ECs and 70.8% of SSTs). The unresolved SLS tumors (13.1%) comprised tumors with only a single somatic (7.3%) or no somatic (5.8%) MMR gene mutations. A tumor-focused testing approach reclassified 86.9% of SLS into Lynch syndrome, sporadic dMMR or MMR-proficient cases. These findings support the incorporation of tumor sequencing and alternate MLH1 methylation assays into clinical diagnostics to reduce the number of SLS patients and provide more appropriate surveillance and screening recommendations.
Cross‐cultural adaptation and validation of the Chinese version of the ankle joint functional assessment tool (AJFAT) questionnaire
Authors: Li Jinfeng , Qiu Fanji , Legerlotz Kirsten
Published: April 2023

Background

Ankle joint functional assessment tool (AJFAT) is gradually becoming a popular tool for diagnosing functional ankle instability (FAI). However, due to the lack of standard Chinese versions of AJFAT and reliability and validity tests, the use of AJFAT in the Chinese population is limited. This study aimed to translate and cross‐culturally adapt the AJFAT from English into Chinese, and evaluate the reliability and validity of the Chinese version of AJFAT and to investigate its psychometric properties.

Methods

The translation and cross‐cultural adaptation of AJFAT was performed according to guidelines for cross‐cultural adaptation of self‐report measures. 126 participants with a history of ankle sprain completed the AJFAT‐C twice within 14 days and completed the Cumberland ankle instability tool (CAIT‐C) once. Test–retest reliability, internal consistency, ceiling and floor effects, convergent and structure validity and discriminative ability were investigated.

Results

The test–retest reliability (ICC = 0.91, 95%CI = 0.87–0.94) and internal consistency (Cronbach's alpha = 0.87) of the AJFAT‐C were excellent. No ceiling or floor effects were detected. A moderate correlation between the AJFAT‐C and the CAIT‐C suggested a moderate convergent validity. The AJFAT‐C had a two‐factor structure: 1. function of the unstable side of the ankle joint (9 items) and 2. symptoms of the unstable side of the ankle (2 items). The ideal cut‐off point of the AJFAT‐C was calculated as 26 points.

Conclusion

The Chinese version of AJFAT can be considered as a valid and reliable ankle joint function evaluation tool that can be applied in clinical and research work.
The impact of sewage effluents on water quality of Lake Hawassa, Ethiopia
Authors: Tibebe Dessie , Tesfaye Yemane , Kassa Yezbie
Published: April 2023

The physicochemical characteristics of water samples from Lake Hawassa was determined with the aim of pointing out possible impacts of industrial effluents, agricultural chemicals and domestic sewage on the water quality of the lake. For this, a total of 15 physicochemical parameters were measured in 72 water samples collected from four different locations on the lake that are adjacent to areas involved in various human activities including agriculture (Tikur Wuha), resort hotel (Haile Resort), public recreation (Gudumale) and referral hospital (Hitita). Samples were collected over a period of six months covering the dry and wet seasons in 2018/19. One-way analysis of variance revealed the presence of significant difference in the physicochemical quality of the lake’s water across the four study areas and the two seasons. Principal component analysis identified the most discriminating characteristics that differentiate the studied areas according to the nature and level of pollution status. Tikur Wuha area was found to be characterized by high levels of EC and TDS, the values of these parameters were about twice or more than that measured in the other areas. This was ascribed to contamination of the lake by runoff water from the surrounding farmlands. On the other hand, the water around the other three areas was characterized by high nitrate, sulfate and phosphate. Hierarchical cluster analysis classified the sampling areas in to two groups, where Tikur Wuha constituted one group and the other three locations the second group. Linear discriminant analysis provided 100% correct classification of the samples into the two cluster groups. The measured values of turbidity, fluoride and nitrate were found to be significantly higher than the standard limits set by national and international guidelines. These results show that the lake has been facing serious pollution problems from various anthropogenic activities.
Inulin diet uncovers complex diet-microbiota-immune cell interactions remodeling the gut epithelium
Authors: Corrêa Renan Oliveira , Castro Pollyana Ribeiro , Fachi José Luís , Nirello Vinícius Dias , El-Sahhar Salma , Imada Shinya , Pereira Gabriel Vasconcelos , Pral Laís Passariello , Araújo Nathália Vitoria Pereira , Fernandes Mariane Font , Matheus Valquíria Aparecida , de Souza Felipe Jaqueline , dos Santos Pereira Gomes Arilson Bernardo , de Oliveira Sarah , de Rezende Rodovalho Vinícius , de Oliveira Samantha Roberta Machado , de Assis Helder Carvalho , Oliveira Sergio Costa , Dos Santos Martins Flaviano , Martens Eric , Colonna Marco , Varga-Weisz Patrick , Vinolo Marco Aurélio Ramirez
Published: April 2023

Background

The continuous proliferation of intestinal stem cells followed by their tightly regulated differentiation to epithelial cells is essential for the maintenance of the gut epithelial barrier and its functions. How these processes are tuned by diet and gut microbiome is an important, but poorly understood question. Dietary soluble fibers, such as inulin, are known for their ability to impact the gut bacterial community and gut epithelium, and their consumption has been usually associated with health improvement in mice and humans. In this study, we tested the hypothesis that inulin consumption modifies the composition of colonic bacteria and this impacts intestinal stem cells functions, thus affecting the epithelial structure.

Methods

Mice were fed with a diet containing 5% of the insoluble fiber cellulose or the same diet enriched with an additional 10% of inulin. Using a combination of histochemistry, host cell transcriptomics, 16S microbiome analysis, germ-free, gnotobiotic, and genetically modified mouse models, we analyzed the impact of inulin intake on the colonic epithelium, intestinal bacteria, and the local immune compartment.

Results

We show that the consumption of inulin diet alters the colon epithelium by increasing the proliferation of intestinal stem cells, leading to deeper crypts and longer colons. This effect was dependent on the inulin-altered gut microbiota, as no modulations were observed in animals deprived of microbiota, nor in mice fed cellulose-enriched diets. We also describe the pivotal role of γδ T lymphocytes and IL-22 in this microenvironment, as the inulin diet failed to induce epithelium remodeling in mice lacking this T cell population or cytokine, highlighting their importance in the diet-microbiota-epithelium-immune system crosstalk.

Conclusion

This study indicates that the intake of inulin affects the activity of intestinal stem cells and drives a homeostatic remodeling of the colon epithelium, an effect that requires the gut microbiota, γδ T cells, and the presence of IL-22. Our study indicates complex cross kingdom and cross cell type interactions involved in the adaptation of the colon epithelium to the luminal environment in steady state.
Data gathering and utilization: humanitarian targeting and ethical issues in northeastern Nigeria
Authors: Fayehun Olufunke , Akanle Olayinka , Popoola Omolara , Okewumi Ewajesu , Williams Funke , Adam Abubakar , Alhajimai Kaka , Abimbola Olufunto
Published: April 2023

Introduction

There are lapses in Nigeria’s data ecosystems with the consequences of imprecise and inaccurate data on humanitarian crises limiting accurate interventions. Therefore, we examined the data targeting processes in the humanitarian sector of Northeast Nigeria and the ethical concerns that arise when such data is collected and used to advance understanding and improve humanitarian protection systems.

Methods

The fieldwork was done in two phases in Maiduguri Borno, North-East Nigeria, between 2021 and 2022. This period was selected because it was the climax of IDP camps in the Northeastern part of the country. Maiduguri was selected for the study because it is the capital of Borno state which is the epicenter of insurgency and internal displacements in Nigeria. Hence, a lot of the most vibrant IDP camps in Nigeria were in Maiduguri for care and security reasons. Fifty in-depth interviews were conducted among the displaced persons across five camps. We also interviewed twenty stakeholders and practitioners working with IDPs to understand Nigeria’s data-based humanitarian contexts of internal displacement. The interviews were tape-recorded and transcribed verbatim by a language expert. The data were coded, and content analyzed to provide context and explore significant operational and ethical issues in data-driven humanitarian protection.

Results

There are discrepancies in the definition of vulnerability in data gathering, putting into question how targeting is carried out to identify vulnerable people and its implications for exclusion. Different data banks and reliability issues across institutions and actors make room for a multiplicity of data and problematic synergy relative to data and ethics. Inconsistent ethical systems guide data gathering and utilization in IDP camps; for instance, there are ineffective norms of recording and securing informed consent during data gathering. States, partners, and IDP camps confront debilitating capacity gaps and equipment deficits that make updated data gathering, storing, retrieval, and utilization. Paper and digital data storage processes were often used with restricted access to only a few key stakeholders. There is vast data expropriation without standard recourse to justice and beneficence as ethical procedures in the humanitarian data space of northeastern Nigeria as a microcosm of Sub-Saharan African realities.

Conclusion

There are enormous implications for effective and efficient targeting processes and outcomes, strategic inclusion, and ethical practices in conflict management, humanitarian interventions, and internal displacement in sub-Saharan Africa.
Randomized Phase II Trial Comparing Bevacizumab Plus Carboplatin and Paclitaxel With Carboplatin and Paclitaxel Alone in Previously Untreated Locally Advanced or Metastatic Non-Small-Cell Lung Cancer
Authors: Johnson David H. , Fehrenbacher Louis , Novotny William F. , Herbst Roy S. , Nemunaitis John J. , Jablons David M. , Langer Corey J. , DeVore Russell F. , Gaudreault Jacques , Damico Lisa A. , Holmgren Eric , Kabbinavar Fairooz
Published: April 2023

PURPOSE

To investigate the efficacy and safety of bevacizumab plus carboplatin and paclitaxel in patients with advanced or recurrent non-small-cell lung cancer.

PATIENTS AND METHODS

In a phase II trial, 99 patients were randomly assigned to bevacizumab 7.5 (n = 32) or 15 mg/kg (n = 35) plus carboplatin (area under the curve = 6) and paclitaxel (200 mg/m2) every 3 weeks or carboplatin and paclitaxel alone (n = 32). Primary efficacy end points were time to disease progression and best confirmed response rate. On disease progression, patients in the control arm had the option to receive single-agent bevacizumab 15 mg/kg every 3 weeks.

RESULTS

Compared with the control arm, treatment with carboplatin and paclitaxel plus bevacizumab (15 mg/kg) resulted in a higher response rate (31.5% v 18.8%), longer median time to progression (7.4 v 4.2 months) and a modest increase in survival (17.7 v 14.9 months). Of the 19 control patients that crossed over to single-agent bevacizumab, five experienced stable disease, and 1-year survival was 47%. Bleeding was the most prominent adverse event and was manifested in two distinct clinical patterns; minor mucocutaneous hemorrhage and major hemoptysis. Major hemoptysis was associated with squamous cell histology, tumor necrosis and cavitation, and disease location close to major blood vessels.

CONCLUSION

Bevacizumab in combination with carboplatin and paclitaxel improved overall response and time to progression in patients with advanced or recurrent non-small-cell lung cancer. Patients with nonsquamous cell histology appear to be a subpopulation with improved outcome and acceptable safety risks.