bluuebunny/crossref_metadata_2025_split huggingface dataset:
Allosteric coupling of substrate binding and proton translocation in MmpL3 transporter from
Mycobacterium tuberculosis
Authors: Babii Svitlana , Li Wei , Yang Lixinhao , Grzegorzewicz Anna E. , Jackson Mary , Gumbart James C. , Zgurskaya Helen I. 
Published: August 2024

ABSTRACT

Infections caused by
Mycobacterium
spp. are very challenging to treat, and multidrug-resistant strains rapidly spread in human populations. Major contributing factors include the unique physiological features of these bacteria, drug efflux, and the low permeability barrier of their outer membrane. Here, we focus on MmpL3 from
Mycobacterium tuberculosis
, an essential inner membrane transporter of the resistance–nodulation–division superfamily required for the translocation of mycolic acids in the form of trehalose monomycolates (TMM) from the cytoplasm or plasma membrane to the periplasm or outer membrane. The MmpL3-dependent transport of TMM is essential for the growth of
M. tuberculosis in vitro
, inside macrophages, and in
M. tuberculosis-
infected mice. MmpL3 is also a validated target for several recently identified anti-mycobacterial agents. In this study, we reconstituted the lipid transport activity of the purified MmpL3 using a two-lipid vesicle system and established the ability of MmpL3 to actively extract phospholipids from the outer leaflet of a lipid bilayer. In contrast, we found that MmpL3 lacks the ability to translocate the same phospholipid substrate across the plasma membrane indicating that it is not an energy-dependent flippase. The lipid extraction activity was modulated by substitutions in critical charged and polar residues of the periplasmic substrate-binding pocket of MmpL3, coupled to the proton transfer activity of MmpL3 and inhibited by a small molecule inhibitor SQ109. Based on the results, we propose a mechanism of allosteric coupling wherein substrate translocation by MmpL3 is coupled to the energy provided by the downhill transfer of protons. The reconstituted activities will facilitate understanding the mechanism of MmpL3-dependent transport of lipids and the discovery of new therapeutic options for
Mycobacterium
spp. infections.

IMPORTANCE

MmpL3 from
Mycobacterium tuberculosis
is an essential transporter involved in the assembly of the mycobacterial outer membrane. It is also an important target in undergoing efforts to discover new anti-tuberculosis drugs effective against multidrug-resistant strains spreading in human populations. The recent breakthrough structural studies uncovered features of MmpL3 that suggested a possible lipid transport mechanism. In this study, we reconstituted and characterized the lipid transport activity of MmpL3 and demonstrated that this activity is blocked by MmpL3 inhibitors and substrate mimics. We further uncovered the mechanism of how the binding of a substrate in the periplasmic domain is communicated to the transmembrane proton relay of MmpL3. The uncovered mechanism and the developed assays provide new opportunities for mechanistic analyses of MmpL3 function and its inhibition.
Whole-genome sequence and annotation of
Diaporthe australafricana
strain CBS 118571
Authors: Li Xin , Wang Xinyi , Li Limei , Lei Rong 
Published: August 2024

ABSTRACT

We report the whole-genome sequence of
Diaporthe australafricana
Crous & J.M. van Niekerkusing using Oxford Nanopore long-read sequencing and Illumina short-read sequencing. The hybrid genome consists of 11 contigs with a total length of 53.509 Mb, and a GC content of 52.40%.
Probing the function of C-terminal region of recombinant α-amylase BmaN1 from
Bacillus megaterium
NL3
Authors: Frima Fina Khaerunnisa , Thufail Muhammad Akbar , Madhani Indri Novia , Nafisah Zahrotun , Shofiyah Sofi Siti , Ulpiyana Ayra , Puspasari Fernita , Aditama Reza , Ihsanawati Ihsanawati , Natalia Dessy 
Published: August 2024

ABSTRACT

The α-amylase BmaN1 from
Bacillus megaterium
NL3 is a member of GH13_45 subfamily that has a conserved C-terminal region of approximately 30 residues. This region features a motif of five aromatic amino acids predicted to play a role in starch binding. This study aimed to unravel the role of the C-terminal region in starch hydrolysis. The full-length and C-terminally truncated forms of BmaN1 (BmaN1∆C) were expressed in
Escherichia coli
ArcticExpress (DE3), resulting in proteins with molecular weights of 56 kDa and 49 kDa, respectively. They exhibited comparable enzymatic activity in the hydrolysis of soluble starch, displaying versatility across a wide range of pH values, temperatures, and NaCl concentrations. BmaN1 and BmaN1∆C activities were inhibited by acarbose and were reduced by SDS and EDTA. In terms of binding and degrading the starch granules, BmaN1∆C showed lower affinity and activity in comparison to BmaN1. Our study indicates that the C-terminal region of BmaN1 significantly enhances its binding affinity and degrading the raw starches.

IMPORTANCE

α-Amylase (EC 3.2.1.1) stands as an endo-acting enzyme, essential for catalyzing the hydrolysis of α-1,4 glycosidic bonds within starch molecules. The relevance of α-amylases in biotechnological applications is substantial, constituting approximately 30% of the global enzyme market. Among these enzymes, BmaN1 was the first α-amylase identified to possess distinct catalytic residues within the GH13 family. BmaN1 from
B. megaterium
NL3 belongs to the GH13_45 subfamily. This subfamily is characterized by a conserved C-terminal region consisting of approximately 30 residues that contains a motif of five aromatic residues predicted to be involved in starch binding. Our study shows that the C-terminal effectively contributes to binding and degrading the raw starch granules. This pioneering research on BmaN1 expands our understanding of α-amylases and holds promise for innovative biotechnological advancements.
Synthesis and Spectral Properties of Conjugated Bis-1,3-diketo Derivatives of Calix[4]arene in the 1,3-alternate Isomeric Form and Their Complexes with Eu3+
Authors: Shvedova А. E. , Deltsov I. D. , Sudakova S. N. , Masliy A. N. , Syakaev V. V. , Vatsouro I. M. , Mambetova G. Sh. , Kuznetsov A. M. , Kovalev V. V. , Mustafina A. R. , Podyachev S. N. 
Published: August 2024

Abstract
Distally substituted bis-1,3-diketone derivatives of calix[4]arene were synthesized, in which chelate groups are attached via a carbonyl carbon atom to the p-positions of phenolic fragments of a macrocycle fixed in 1,3-alternate isomeric form. 1,3-Diketone derivatives were obtained by acylation of magnesium enolate of a calix[4]arene ketone with 1-benzoylbenzotriazoles. In the synthesized compounds, 1,3-diketone groups are conjugated with the π-aromatic system of calix[4]arene. It was found by means of UV spectroscopy and NMR diffusion methods in combination with quantum chemical (DFT) calculations that a mononuclear complex with bis-chelate coordination of the lanthanide ion is predominantly formed in the solution. The formation of the complex leads to a decrease in the conjugation degree in the ligand. The most effective sensitization of Eu3+ luminescence, compared to the p-F- or p-CF3-phenyl-substituted complexes is observed for calix[4]arene complexes with H-phenyl-substituted 1,3-diketone groups.
Unilateral tongue swelling: an unusual presentation of angiotensin-converting enzyme inhibitor-related angioedema
Authors: Eloff Julian Robert Paul , Oosthuizen Almero 
Published: August 2024

Angioedema is a rare but potentially fatal complication of angiotensin-converting enzyme inhibitor (ACEi) treatment. This class of drugs is widely used in the treatment of hypertension, cardiac failure and other common conditions.This case report discusses a male patient in his 60s who presented with acute swelling of the right side of his tongue, an unusual manifestation of angioedema, which typically involves bilateral swelling of orofacial structures.Accurate and early identification of this complication affords the opportunity for early, potentially life-saving intervention during the acute episode and also cessation of the treatment, reducing the risk of recurrence in the future.This case is one of only a few reported in English language medical literature and the first from Africa, suggesting either rarity or under-reporting. The case contributes to the understanding of ACEi-induced angioedema, particularly in Africa where hypertension is prevalent and ACEi is commonly used.
Modified nasopharyngeal airway for pressure support ventilation in airway management of a case of Robin sequence with bilateral temporomandibular joint ankylosis
Authors: Kumar Abhyuday , Kumari Babli , Kumar Ajeet , Kumar Neeraj 
Published: August 2024

The association of Robin sequence (RS) with temporomandibular joint (TMJ) ankylosis is not a common occurrence. Due to restricted mouth opening, difficult bag valve mask ventilation and difficult intubation, such cases are always challenging for anaesthesiologists.A male patient in early childhood with RS and bilateral TMJ ankylosis was scheduled for bilateral gap arthroplasty. Airway management was planned with fibreoptic intubation under sedation to preserve spontaneous ventilation. After sedating the patient, a nasopharyngeal airway modified by using an endotracheal tube connector was inserted in the left nostril and connected to the ventilator circuit with a 15 mm universal connector. Pressure support ventilation was given with continuous end-tidal CO2monitoring. Fibreoptic intubation was done through the right nostril with maintenance of spontaneous ventilation.Nasal pressure support ventilation assembly can be made with available equipment in the operation theatre. It can be a substitute for a high-flow nasal cannula in particular cases.
Novel hyperparallel optical coherence tomography for angle closure assessment: comparison with swept-source OCT and gonioscopy
Authors: Porporato Natalia , Xu Benjamin Y , Tan Bingyao , Chang Yu Q , Tun Tin A , Perera Shamira , Husain Rahat , Ho Ching Lin , Sultana Rehena , Aung Tin , Schmetterer Leopold 
Published: August 2024

Aim
To evaluate reproducibility and agreement of angle closure assessment by a novel hyperparallel optical coherence tomography (OCT) system (HP-OCT, Cylite Optics, Melbourne, Australia), in comparison with swept-source OCT (SS-OCT, CASIA SS-1000, Tomey Corporation, Nagoya, Japan) and gonioscopy.

Methods
Cross-sectional study. Phakic subjects >40 years, with no relevant ophthalmic history were consecutively recruited from the glaucoma clinic. Subjects underwent same-day evaluation with HP-OCT, SS-OCT and gonioscopy. The primary outcome was the presence of angle closure, defined as iridotrabecular contact in HP-OCT and SS-OCT images at 0°−180° meridional and as non-visibility of the posterior trabecular meshwork (TM) by gonioscopy. Visibility of TM was also assessed (secondary outcome). Intra and interdevice agreement analysis (Gwet AC1) and logistic regression analysis were performed for primary and secondary outcomes, respectively.

Results
154 sectors from horizontal scans of 77 subjects were analysed. The reproducibility of angle closure assessment by HP-OCT was excellent (AC1 of 0.95 for temporal angle and 1.00 for nasal). Agreement for angle closure detection was very good between HP-OCT and SS-OCT (AC1 of 0.88 for temporal and 0.81 for nasal angle) and good between HP-OCT and gonioscopy (AC1 of 0.71 for temporal and 0.78 for nasal angle). TM was identifiable in 64.4% (94/146) of unprocessed HP-OCT images (both open and closed angles), however not visible in any of the SS-OCT unprocessed images.

Conclusions
HP-OCT showed excellent reproducibility for angle closure assessment and good agreement with SS-OCT and gonioscopy. HP-OCT technology also provides a unique capability to visualise regions around TM and Schlemm’s canal, opening new avenues for clinical research of distal outflow pathways.
The effectiveness of intratympanic injections with methylPREDnisolon versus placebo in the treatment of vertigo attacks in MENière’s disease (PREDMEN trial): a study protocol for a phase-3 multicentre, double-blinded, randomised, placebo-controlled trial
Authors: Boreel Maud Martina Emilie , van Esch Babette , Schermer Tjard R , Mol Berber M , van Benthem Peter Paul , Bruintjes Tjasse D 
Published: August 2024

IntroductionIntratympanic corticosteroids are commonly used in the treatment of Menière’s disease (MD). However, few and small randomised controlled trials (RCT) on the effectiveness of intratympanic corticosteroids have been performed. A recent Cochrane review suggested that a well-conducted placebo-controlled RCT with a large study population is required to evaluate the effectiveness of the use of intratympanic corticosteroids in MD. The following protocol describes a phase-3 multicentre, double-blinded, randomised, placebo-controlled trial to compare the effectiveness of methylprednisolone (62.5 mg/mL) to a placebo (sodium chloride 0.9%).Methods and analysisWe aim to recruit 148 patients with unilateral MD from six hospitals in the Netherlands. Patients will be randomly assigned to either the methylprednisolone or the placebo group. Two injections will be given, one at baseline and one after 2 weeks. Follow-up assessments will be done at 3, 6, 9 and 12 months. The primary outcome will be the frequency of vertigo attacks. Attacks will be evaluated daily with the DizzyQuest app. Secondary outcomes include hearing loss, tinnitus, health-related quality of life, use of co-interventions and escape medication, (serious) adverse events and cost-effectiveness. These will be evaluated with audiometry and multiple commonly used, validated questionnaires. For the primary and secondary outcomes mixed model analysis, generalised estimating equation analysis and logistic regression analysis will be used.Ethics and disseminationThis study was submitted via the Clinical Trials Information System, reviewed and approved by the Medical Research Ethics Committee Leiden The Hague Delft and the local institutional review board of each participating centre. All data will be presented ensuring the integrity and anonymity of patients. Results will be published in scientific journals and presented on (inter)national conferences.Trial registration numberThis study is registered at ClinicalTrials.gov Protocol Registration and Results System, with the registration ID:NCT05851508.
Validation of the Employment Precariousness Scale and its associations with mental health outcomes: results from a prospective community-based study of pregnant women and their partners in Dresden, Germany
Authors: Karl Marlene , Staudt Andreas , Vives Alejandra , Kopp Marie , Weise Victoria , Mack Judith T , Steudte-Schmiedgen Susann , Seidler Andreas , Garthus-Niegel Susan 
Published: August 2024

ObjectiveTo translate the Employment Precariousness Scale (EPRES) from Spanish into German (EPRES-Ge), adapt it to the German context, assess the psychometric properties and show prospective associations with mental health outcomes within the peripartum period.DesignAnalyses encompassed descriptive statistics, exploratory factor analysis, confirmatory factor analysis (CFA) to validate the structure of the EPRES, and multivariate regression analyses with mental health outcomes 8 weeks after birth.ParticipantsSelf-report data from 3,455 pregnant women and their partners within the Dresden Study on Parenting, Work, and Mental Health prospective longitudinal cohort study were used.ResultsThe EPRES-Ge with five dimensions and 20 items showed good internal consistency (Cronbach’s α=0.77). All scales showed good reliability coefficients of α=0.73–0.85 and good item-subscale correlations of r=0.63–0.98, with the exception of subscale rights, which showed poor reliability of α=0.30 and item-subscale correlations of r=0.45–0.68. Exploratory analysis and CFA confirmed the proposed five-dimensional structure, explaining 45.08% of the cumulative variance. Regression analyses with mental health outcomes after birth revealed statistically significant associations (β=0.12–0.20).ConclusionsThe EPRES-Ge is a valuable tool for assessing employment precariousness as a multidimensional construct. The scales could be adapted to the German working context. Precarious employment, as measured by the EPRES-Ge, is a determinant of mental health problems in young families.
Prevention and care of adult enterostomy with high output: a scoping review protocol
Authors: Che Ying , Wang Tianming , Gao Caifeng , Sun Fei , Li Shangke , Luo Zhanlin 
Published: August 2024

IntroductionThe purpose of this protocol is to investigate the risk factors, critical evaluation contents and preventive measures of high-output enterostomy.Methods and analysisThis scoping review will follow the Joanna Briggs Institute guidelines for scoping reviews. PubMed, EMBASE, CINAHL, the Chinese Biological Literature Database and the Cochrane Library will be searched for relevant literature published from January 2015 to January 2024. The Grading of Recommendations, Assessment, Development and Evaluation and the Risk Of Bias In Non-randomised Studies of Interventions will be used to assess the reliability of the evidence.Ethics and disseminationAs this scoping review involves database searches for literature analysis, informed consent and ethical approval from patients will not be required. The findings will provide essential decision-making information for researchers, clinicians and ostomy nursing staff. The results of the review will be presented at a scientific conference and published in a peer-reviewed journal.
Comparing long-term prognosis following different surgical methods in patients with early stage breast cancer and obesity: a retrospective cohort study in China
Authors: Li Lun , Pang Jian , Yan Yiqing , Zhang Qi , Zheng Shuyue , Chen Ming , Yi Wenjun , Wu Jiong 
Published: August 2024

ObjectiveBreast-conserving therapy (BCT) includes breast-conserving surgery (BCS) combined with radiation therapy (RT). RT plays a crucial role in improving the prognosis of patients who undergo BCS. However, obesity is a potential risk factor for resistance to radiation. The aim of this study was to evaluate any difference in the long-term prognosis of patients with early stage breast cancer and obesity treated with BCT or total mastectomy (TM).Design, setting and participantsThis was a retrospective cohort study involving 1125 patients diagnosed with early stage breast cancer and obesity at the Shanghai Cancer Center of Fudan University from 2013 to 2016.Outcome measuresObesity in the Chinese population was defined as a body mass index ≥28 kg/m2. Surgical options included BCT and TM. The primary survival outcomes were overall survival (OS), disease-free survival (DFS) and recurrence-free survival (RFS). Inverse probability of treatment weighting (IPTW) was used to control for the impact of confounding factors on prognosis.ResultsThe median follow-up times in the BCT group and TM group without postoperative RT were 51.1 months (IQR of 40.6–68.1 months) and 61.8 months (IQR of 46.5–76.7 months), respectively. After IPTW, the baseline data were balanced. Compared with those in the TM cohort, patients in the whole IPTW cohort in the BCT cohort had worse DFS (HR 4.280, 95% CI 2.180 to 8.400; p<0.001), RFS (HR 4.380, 95% CI 2.370 to 8.120; p<0.001) and OS (HR 3.590, 95% CI 1.620 to 7.950; p=0.002).ConclusionIn patients with early stage breast cancer and obesity, TM is associated with better survival outcomes than BCT.
Machine learning-derived phenotypic trajectories of asthma and allergy in children and adolescents: protocol for a systematic review
Authors: Lisik Daniil , Milani Gregorio Paolo , Salisu Michael , Özuygur Ermis Saliha Selin , Goksör Emma , Basna Rani , Wennergren Göran , Kankaanranta Hannu , Nwaru Bright I 
Published: August 2024

IntroductionDevelopment of asthma and allergies in childhood/adolescence commonly follows a sequential progression termed the ‘atopic march’. Recent reports indicate, however, that these diseases are composed of multiple distinct phenotypes, with possibly differential trajectories. We aim to synthesise the current literature in the field of machine learning-based trajectory studies of asthma/allergies in children and adolescents, summarising the frequency, characteristics and associated risk factors and outcomes of identified trajectories and indicating potential directions for subsequent research in replicability, pathophysiology, risk stratification and personalised management. Furthermore, methodological approaches and quality will be critically appraised, highlighting trends, limitations and future perspectives.Methods and analyses10 databases (CAB Direct, CINAHL, Embase, Google Scholar, PsycInfo, PubMed, Scopus, Web of Science, WHO Global Index Medicus and WorldCat Dissertations and Theses) will be searched for observational studies (including conference abstracts and grey literature) from the last 10 years (2013–2023) without restriction by language. Screening, data extraction and assessment of quality and risk of bias (using a custom-developed tool) will be performed independently in pairs. The characteristics of the derived trajectories will be narratively synthesised, tabulated and visualised in figures. Risk factors and outcomes associated with the trajectories will be summarised and pooled estimates from comparable numerical data produced through random-effects meta-analysis. Methodological approaches will be narratively synthesised and presented in tabulated form and figure to visualise trends.Ethics and disseminationEthical approval is not warranted as no patient-level data will be used. The findings will be published in an international peer-reviewed journal.PROSPERO registration numberCRD42023441691.
Risk factors for acute kidney injury and impact of earlier anticoagulation on renal function in patients with normotensive pulmonary embolism: a retrospective cohort study
Authors: Wang Dingyi , Fan Guohui , Lyu Yanshuang , Xu Xiaomao , Luo Qin , Wan Jun , Liu Xin , Chen Yinong , Zhang Yu , Yang Peiran , Zhai Zhenguo 
Published: August 2024

ObjectiveWe aimed to investigate the risk factors for acute kidney injury (AKI) after normotensive pulmonary embolism (PE) and the impact of anticoagulation on renal recovery.DesignMulticentred, retrospective cohort study.SettingData from four tertiary hospitals in China were captured. All available measurements of serum creatinine (SCr) during hospitalisation and follow-up were collected.ParticipantsPatients with acute PE and those without haemodynamic instability were enrolled. All recruited patients were followed up for up to 2 years.Primary and secondary outcome measuresThe primary outcome was the occurrence of AKI, defined by the Kidney Disease Improving Global Outcomes criteria. The secondary outcome was the recovery of renal function. The time interval between PE onset and the initiation of anticoagulation was analysed to obtain its influence on the recovery of renal function.ResultsA total of 461 patients with acute normotensive PE were enrolled. A transient elevation of SCr during hospitalisation was observed. The incidence of AKI among normotensive patients was 18.9%. Brain natriuretic peptide (BNP) NT-proBNP elevation (adjusted HR (aHR) 2.27, 95% CI 1.33 to 3.86) and history of chronic kidney disease (aHR 4.81, 95% CI 2.44 to 9.48) were associated with the development of AKI during hospitalisation. Earlier initiation of anticoagulation therapy (within 5 days after PE onset, compared with over 6 days) promoted an early recovery of renal function (adjusted OR 0.26, 95% CI 0.08 to 0.84, p=0.025).ConclusionsRenal impairment and AKI were highly prevalent among patients with normotensive patients. The occurrence of AKI was associated with right heart function. Patients who developed AKI after PE would benefit from earlier anticoagulation therapy for an early recovery of renal function.