bluuebunny/crossref_metadata_2025 huggingface dataset:
Hearing Loss and Autism Spectrum Disorder
Authors: Pollick Sarah A. , Pesch Megan Honor , Spellun Arielle , Betances Elodie M. , Wiley Susan , Geer Leah C. , Prout Kerry K. , Hu Michelle , Nyp Sarah S.
Published: August 2024

CASE:

Gretta is a 3.5-year-old girl with a history of congenital cytomegalovirus, congenital bilateral profound sensorineural hearing loss (SNHL), and bilateral vestibular dysfunction, resulting in frequent falls. She underwent cochlear implantation at 12 months of age and was diagnosed with autism spectrum disorder at 2.5 years of age.

On presentation for follow-up in the developmental-behavioral pediatrics (DBP) clinic, Gretta's mother reports that Gretta has refused to wear her cochlear implants for the past 5 months. Before that, she seemed to enjoy having access to sound and like dancing to music, and her receptive and expressive language skills, including speech, were progressing. Initially, the rejection of her devices occurred only at preschool. When frustrated or overwhelmed, she would close her eyes and remove her devices for up to 5 minutes before allowing them to be reapplied. Over time, this progressed to a complete refusal to wear her devices at school and then at home, rendering her without access to sound and spoken language.

Gretta's mood has become sullen, and she is now having tantrums at school. She physically startles when attempts are made to reintroduce her devices. Her ability to participate in classroom learning or interact with her classmates is limited, as she attends a spoken-language–focused preschool program. A board-certified behavioral analyst, hired by the family, recommended that Gretta not be allowed to participate in classroom activities unless she wears her devices. She now becomes visibly anxious even when in the same room as her devices and repetitively states “no implant, no implant.” Her mother is worried about her inability to communicate and has “no idea” what may have changed or sparked her initial refusal to wear the devices.

What factors would you consider when determining the cause and function of Gretta's refusal to wear the cochlear implants? How would you guide her parents, teachers, and clinicians to ensure the best developmental and behavioral outcomes for her?
Compliance With International Council of Ophthalmology Guidelines for Glaucoma Eye Care in Pakistan
Authors: Mahsood Yousaf Jamal , Nasir Ali Hassan , Wakil Hira , Farooq Saima
Published: August 2024

Précis:

This study demonstrated that the compliance levels with International Council of Ophthalmology (ICO) Guidelines for glaucoma eye care were low for all the elements in both public and private health care settings.

Purpose:

To determine the compliance with the ICO guidelines for glaucoma eye care among Pakistani ophthalmologists and to compare differences among ophthalmologists practicing in public and private health care settings.

Materials and Methods:

This was a retrospective chart review, and the records were reviewed according to ICO guidelines. The ICO recommends that each patient with glaucoma be evaluated for 19 items from 3 elements which are history, examination, and investigations. Mean compliance was recorded for each of the 3 elements. The compliance of each item was also checked and then a compared between the 2 settings, that is, public and private health care settings.

Results:

A total of 394 records were analyzed, with a mean age of 51.9±14.9 years and 232 (58.9%) male patients. Most records were from private settings 339 (86%), and primary open angle glaucoma 163 (41.4%) was the most common diagnosis. Compliance was low for all elements; history (31.8%), examination (61.3%), and investigation (6%). Pupil reaction differed significantly between the 2 groups (P=0.001).

Conclusion:

Pakistan’s ophthalmologists, whether in public or private health care settings, lack knowledge of ICO guidelines for glaucoma eye care. This study emphasizes the importance of implementing these guidelines in the general ophthalmology curriculum.
Patients’ Acceptance of Glaucoma Therapy in Sub-Saharan Africa
Authors: Olawoye Olusola , Sarimiye Tarela , Washaya Jennifer , Gessesse Girum W. , Balo Komi , Agre Jeremie , Macheka Boniface , Kizor-Akaraiwe Nkiru , Pons Jonathan , Ashaye Adeyinka , Garba Farouk , Chitedze Richard , Ibanga Affiong , Mahdi Abdull , Ogunro Adunola , Budengeri Patrick , Ajibode Haroun Adetunji , Tamrat Lemlem , Onakoya Adeola , Okeke Suhanyah , Giorgis Abeba T. , Okosa Chimdi Chuka , Fowobaje Kayode , Cook Stephen , Lawrence Scott , Chan Ving Fai , Blanco Augusto Azuara , Congdon Nathan , Realini Tony ,   The STAGE Research Group
Published: August 2024

Précis:

Patients’ acceptance of glaucoma therapy was high overall in this study, but lower for surgery than for laser or medical therapy. Fear and cost were the leading reasons why patients declined recommended therapy and they were treatment-specific. Cost was the primary reason for declining medical and laser therapy, while fear was the most common reason for declining surgical therapy.

Purpose:

To determine the frequency at which patients newly diagnosed with glaucoma in sub-Saharan Africa (SSA) decline recommended therapy and to characterize the reasons for declining therapy.

Methods:

This was a multicenter, cross-sectional study conducted on adult patients at the time of glaucoma diagnosis at 27 centers in 10 countries in SSA. Data collected from the diagnostic encounter included demographics, clinical glaucoma characteristics, treatment recommendations, patient acceptance of therapy, and reasons for declining therapy.

Results:

Among 2282 eyes of 1198 patients offered treatment for glaucoma, initially recommended treatment was accepted in 2126 eyes (93.2%). Acceptance of therapy varied with the nature of treatment offered, with medical therapy accepted in 99.2% of eyes, laser therapy in 88.3%, and surgical therapy in 69.3%. The most common reasons cited for declining therapy were fear (42.9%) and cost (41.7%); cost was the primary reason for declining medical and laser therapy, while fear was the most common reason for declining surgical therapy. Most patients declining laser or surgical therapy accepted medical therapy as an alternate therapy (98.1%).

Conclusions:

Patients’ acceptance of glaucoma therapy was high overall, but lower for surgery than for laser or medical therapy. Most patients who declined laser or surgical therapy accepted medical therapy as an alternate therapy when offered. Educational interventions, sustainable incentives, and other approaches are needed to enhance patient acceptance of glaucoma therapy in this setting, particularly surgery, when needed.
Perspectives of Caregivers on Children Boarding With Mental Health Conditions
Authors: Collins Samantha C. , Ferrigno Nicholas K. , King Roz , Chumpitazi Corrie E. , Stanley Rachel M. , Pulcini Christian D.
Published: August 2024

Objective

Addressing the acute mental healthcare needs of children is a national crisis. Despite the ongoing crisis, there are limited prior studies that capture caregiver perspectives on acute pediatric mental healthcare, notably in a general emergency department (ED) in a rural state. Based on these knowledge gaps, our objective was to assess caregiver opinions and perspectives of acute management for children boarding with mental health conditions.

Methods

Semistructured interviews were conducted with caregivers of patients (under 18 years old) with a primary mental health condition boarding in a general ED (length of stay ≥24 hours) within a qualitative grounded theory approach. An interview guide was developed a priori and reviewed among key stakeholders. A trained study team performed the interviews. A coding tree was developed through an iterative process that included double-coding transcripts and monitoring of interrater reliability to perform thematic analysis.

Results

Fourteen interviews were conducted to reach thematic saturation. Key themes elicited from caregivers included mental healthcare delivery, access to mental healthcare services, care setting, and level of support for families and caregivers. Most caregivers focused on the following challenges and suggestions: access to appropriate, evidence-based mental healthcare, improved communication between all stakeholders involved, and staff education on mental healthcare for children

Conclusions

Caregivers face considerable challenges in attaining timely and appropriate acute mental health care for their children. Immediate and innovative resource allocation is needed across the healthcare continuum to bolster the acute mental healthcare services currently offered to children and families, especially in the general ED setting.
New Assessment Method of Alveolar Bone Grafting Using Automatic Registration and AI-based Segmentation
Authors: Fujii Yasuyuki , Sugiyama-Tamura Tomoko , Sugisaki Risa , Chujo Yuri , Honda Aya , Kono Michihide , Chikazu Daichi
Published: August 2024

Objective:

The aim of this Technical note is to present a new assessment method of alveolar bone grafts after secondary alveolar bone grafting using automatic registration and artificial intelligence (AI)-based segmentation.

Methods:

A total of 7 Japanese patients (4 men and 3 women) with a unilateral cleft lip, alveolus, and/or palate, who underwent secondary alveolar bone grafting between March 2021 and August 2022 were evaluated. Computed tomography (CT) analyses were performed about 1 month before the surgery, and 1 day and 6 months after the surgery. All CT images were imported into a 3-dimensional analysis workstation. CT images from after the surgery were superimposed onto CT images from before the surgery, by automatic rigid image registration. The segmentation of bone tissues was automatically performed by the AI-based function. Grafted bone was extracted by subtraction of the bone tissue after the surgery from the bone tissue before the surgery. The volumes and Hounsfield units (HUs) of the grafted bones were calculated. The intraclass correlation coefficient (ICC) was reviewed to assess inter-rater reliability.

Results:

The ICCs (2,1) of the volumes and HUs measured by the observers immediately after the surgery were 0.95 and 0.99, respectively. On the other hand, the ICCs (2,1) of the volumes and HUs measured by the observers 6 months after the surgery were 0.81 and 0.57, respectively.

Conclusions:

Our new assessment method enables simple and quick evaluation of residual grafted bone after secondary alveolar bone grafting and demonstrated relatively high inter-rater reliability.
Polysomnogram Findings and Psychosocial and Academic Concerns in Children With Cleft Palate With or Without Cleft Lip
Authors: Riklin Eric , Choi Dylan G. , Trotter Collean , Lasky Sasha , Kato Roberta M. , Davidson Ward Sally L. , Magee William P. , Hammoudeh Jeffrey A. , Urata Mark M. , Johns Alexis L.
Published: August 2024

Children born with a cleft palate with or without a cleft lip (CP±L) are at risk for sleep-disordered breathing, particularly obstructive sleep apnea (OSA). While OSA and CP±L have both been associated with higher risk for psychosocial and academic concerns, their combined risk has been understudied. This paper aimed to describe polysomnography findings and psychosocial and academic concerns among children with isolated (iCP±L) and syndrome-associated (sCP±L) clefts who had undergone primary palatoplasty. Medical records were reviewed from 2004 to 2022 for demographics, medical history, polysomnography results, and family-reported psychosocial and academic variables. Of the 694 patients with CP±L who had a palatoplasty, 147 had a polysomnogram and 82 had at least one follow-up polysomnogram. Across time points, only 19% to 27% of participants had normal polysomnograms and the most frequent finding was mild OSA for 30% to 35% of patients. For children with iCP±L, more frequent oxygen desaturations were significantly associated with receiving special education services and family-reported academic concerns and OSA was associated with a history of receiving mental health services. Children with sCP±L had a significantly higher Obstructive Apnea-Hypopnea Index and a greater proportion of all-day special education classroom placements relative to youth with iCP±L. Study results suggest that cleft providers should monitor for OSA and sleep-disordered breathing symptoms, collaborate with pulmonologists for evaluation and treatment of sleep concerns, and address possible sleep-associated psychosocial and academic issues.
Assessment of Novel Surgical Procedures Using Bone Morphogenic Protein-7 Infused Into Decellularised Muscle and Bioactive Ceramic: A Histological Analysis
Authors: Alfotawi Randa
Published: August 2024

Objective:

Reconstruction of critical bone defects is considered a challenge due to vascular reperfusion injury that may occur. The present study hypothesized that the use of decellularized muscle scaffold (DMS) and bone morphogenic protein-7 (BMP-7), along with resorbable bioactive ceramic silica calcium phosphate cement (SCPC) seeded with human bone marrow stromal cells, can expedite bone formation and maturation.

Methods:

Surgical bone defects were created in 20 nude transgenic mice. In experimental group 1 (n = 10), a critical-size (4 mm) calvarial defect was made and grafted with DMS-BMP-7/SCPC. In situ human bone marrow stromal cells [human mesenchymal stromal cells (hMSC)] were seeded thereafter. As a control, group 2 (n = 10) was treated with DMS/SCPC seeded with hMSCs. After 8 weeks, bone regeneration was evaluated using histology and histomorphometry for both groups.

Results:

Histological examination showed bone regeneration crossing the gap (experimental group 1), bone regeneration was noted at the defect periphery, and scattered islands of bone at the canters of the defects (control group 2). New bone formation and maturation were superior in the groups treated with the DMS/BMP-7/SCPC/hMSC constructs. The quantitative histological assessment revealed that the average bone surface area was 255 ± 25 mm2, which was 1.5 times the surface area of group 2, which was reported at 170 ± 35 mm2. The reported difference was considered statistically significant (P < 0.05).

Conclusion:

The DMS-BMP-7/SCPC scaffold induced bone regeneration and neovascularization in critical-size defects.
Evidence for the Positive Impact of Centralization in Esophageal Cancer Surgery
Authors: Donlon Noel E. , Moran Brendan , Davern Maria , Davey Matthew G. , Kennedy Czara , Leahy Roisin , Moore Jenny , King Sinead , Lowery Maeve , Cunningham Moya , Donohoe Claire L. , O’Toole Dermot , Ravi Narayanasamy , Reynolds John V.
Published: August 2024

Objective:

To analyze the impact of centralization on key metrics, outcomes, and patterns of care at the Irish National Center.

Background:

Overall survival rates for esophageal cancer in the West have doubled in the last 25 years. An international trend towards centralization may be relevant; however, this model remains controversial, with Ireland centralizing esophageal cancer surgery in 2011.

Methods:

All patients (n=1245) with adenocarcinoma of the esophagus or junction treated with curative intent involving surgery, including endoscopic surgery, were included (n=461 from 2000 to 2011, and 784 from 2012 to 2022). All data entry was prospectively recorded. Overall survival was measured (1) for the entire cohort, (2) for patients with locally advanced disease (cT2-3N0-3), and (3) for patients undergoing neoadjuvant therapy. All complications were recorded as per Esophageal Complication Consensus Group definitions, and the Clavien-Dindo severity classification. Data were analyzed using GraphPad Prism (v.6.0) for Windows and SPSS (v.23.0) software (SPSS) R Studio (R version 4.2.2). Survival times were calculated using a log-rank test and Cox regression analysis, and Kaplan-Meier curves were generated.

Results:

Endotherapy for cT1a/intramucosal cancer adenocarcinoma increased from 40 (9% total) to 245 (31% total) procedures between the pre-centralization and post-centralization (post-C) periods. A significantly (P < 0.001) higher proportion of patients with cT2-3N0-3 disease in the post-C period underwent neoadjuvant therapy (66% vs 53%). Operative mortality was lower (P=0.02) post-C, at 2% versus 4.5%, and ≥IIIa Clavien-Dindo major complications decreased from 33% to 25% (P < 0.01). Recurrence rates were lower post-C (38% vs 53%, P < 0.01). Median overall survival was 73.83 versus 47.23 months in the 2012 to 2022 and 2000 to 2011 cohorts, respectively (P < 0.001). For those who received neoadjuvant therapy, the median survival was 28.5 months pre-centralization and 42.5 months post-C (P < 0.001).

Conclusions:

These data highlight improvements in both operative outcomes and survival from the time of centralization, and a major expansion of endoscopic surgery. Although not providing proof, the study suggests a positive impact of formal centralization with governance on key quality metrics and an evolution in patterns of care.
A Meta-analysis of Different Acupuncture Modalities Combined With Antidepressants to Reduce Major Depressive Disorder
Authors: Shu Wanqing , Pan Yongzhen
Published: August 2024

Objectives

Acupuncture is an effective therapy for depression. Nevertheless, the results of clinical studies on major depressive disorder (MDD) remain controversial.

Methods

By November 2023, English-language published randomized clinical trials involving acupuncture for treating MDD were searched. The analysis comprised 9 studies with 809 subjects who met the eligibility criteria. The quality of the included studies was evaluated using the Quality in Prognostic Studies (QUIPS) tool.

Results

Acupuncture moderately alleviated the severity of MDD, independent of the method used (standardized mean difference [SMD] = −0.55; confidence interval [CI] 95%: −1.19, 0.09; P = 0.08). The severity of MDD was moderated by MA, regardless of antidepressant use (SMD = −0.49; CI95%: −1.13, 0.14, P = 0.09). Subgroup analysis revealed a nonsignificant reduction in MDD severity when using manual acupuncture alone (SMD −0.52; CI95%: −1.47, 0.44, P = 0.18). MDD severity was reduced by the use of manual acupuncture and antidepressants (SMD = −0.47; CI95%: −0.88, −0.06). Laser acupuncture and electroacupuncture (with or without antidepressants) did not significantly affect the severity of MDD.

Conclusions

Manual acupuncture with or without antidepressants may alleviate the severity of MDD, but its clinical benefit for treating MDD is inconclusive.
Leaderless consensus decision-making determines cooperative transport direction in weaver ants
Authors: Carlesso Daniele , Stewardson Madelyne , McLean Donald James , Mazué Geoffrey P. F. , Garnier Simon , Feinerman Ofer , Reid Chris R.
Published: August 2024

Animal groups need to achieve and maintain consensus to minimize conflict among individuals and prevent group fragmentation. An excellent example of a consensus challenge is cooperative transport, where multiple individuals cooperate to move a large item together. This behaviour, regularly displayed by ants and humans only, requires individuals to agree on which direction to move in. Unlike humans, ants cannot use verbal communication but most likely rely on private information and/or mechanical forces sensed through the carried item to coordinate their behaviour. Here, we investigated how groups of weaver ants achieve consensus during cooperative transport using a tethered-object protocol, where ants had to transport a prey item that was tethered in place with a thin string. This protocol allows the decoupling of the movement of informed ants from that of uninformed individuals. We showed that weaver ants pool together the opinions of all group members to increase their navigational accuracy. We confirmed this result using a symmetry-breaking task, in which we challenged ants with navigating an open-ended corridor. Weaver ants are the first reported ant species to use a ‘wisdom-of-the-crowd’ strategy for cooperative transport, demonstrating that consensus mechanisms may differ according to the ecology of each species.
When an underestimated zoonosis and antimicrobial resistance collide: Corynebacterium ulcerans
Authors: Mori Giovanni , Errico Giulia , Giancristofaro Sara , Visentin Donatella , Castagna Antonella , Viel Laura , Dellamaria Debora , Lorenzin Giovanni , Ortalli Gaia , Scarparo Claudio , Lanzafame Massimiliano
Published: August 2024

In the European region, diphtheria is now rarely suspected in patients presenting with upper respiratory tract symptoms. C. ulcerans is the underestimated zoonosis that is replacing C. diphtheria infections in industrialised countries. We report a case of macrolide-resistant C. ulcerans infection with no apparent zoonotic transmission and outline the efforts required for public and zooprophylactic management of these cases. We describe the main critical issues to be addressed to comprehensively tackle this zoonosis in the future.
Two new members of the genus Sphingobacterium: Sphingobacterium zhuxiongii sp. nov. and Sphingobacterium luzhongxinii sp. nov.
Authors: Tao Yuanmeihui , Yang Caixin , Dong Kui , Luo Wenbo , Ye Lin , Pu Ji , Yang Jing , Zheng Han , Xu Jianguo
Published: August 2024

Four strains, designated dk4302T, dk4209, xlx-73T, and xlx-183, were isolated from Tibetan gazelle and red swamp crawfish collected from the Qinghai–Tibet Plateau and Jiangxi Province, PR China. The strains were Gram-stain-negative, aerobic, rod-shaped, non-motile, mucoid, and yellow-pigmented. Strains dk4302T and dk4209 grew at 10–40 °C and pH 6.0–9.0, while strains xlx-73T/xlx-183 grew at 15–40 °C and pH 6.0–10.0. Both strains exhibited growth in the presence of up to 3.5 % (w/v) NaCl. Phylogenetic and phylogenomic analyses based on the 16S rRNA gene sequences and 652 core genes, respectively, revealed that the four strains formed two distinct clusters in the genus Sphingobacterium. Strains dk4302T and dk4209 formed a distinct clade with Sphingobacterium hotanense XH4T and Sphingobacterium humi D1T. The most closely related strains to xlx-73T and xlx-183 were Sphingobacterium nematocida M-SX103T. The DNA G+C contents were 38.9 and 39.8 mol%. The digital DNA–DNA hybridization (dDDH) values between dk4302T and S. humi D1T and S. hotanense XH4T were 19.2 and 21.8 % (19.0 and 21.6 % for strain dk4209), respectively. The corresponding average nucleotide identity (ANI) values were 74.3 and 78.1 % (74.4 and 78.3 % for strain dk4209), respectively. The dDDH values between xlx-73T (xlx-183) and S. nematocida M-SX103T was 24.6 % (25.7 %). The corresponding ANI value was 85.7 % (85.5 % for strain xlx-183). The major fatty acid and respiratory quinone of dk4302T and xlx-73T were iso-C15:0 and MK7. The polar lipids identified in all of the novel strains were phosphatidylethanolamine, phosphoglycolipids, aminophospholipids, and phospholipids. A total of 61/190 (32.1 %) and 82/190 (43.2 %) carbon substrates were metabolized by strains dk4302T and xlx-73T in the Biolog MicroPlates, respectively. Based on the results from this polyphasic taxonomic study, two novel species in the genus Sphingobacteruim are proposed, namely Sphingobacteruim zhuxiongii sp. nov. (type strain dk4302T=CGMCC 1.16795T=JCM 33600T) and Sphingobacteruimluzhongxinii sp. nov. (type strain xlx-73T=GDMCC 1.1712T=JCM 33886T).
SARS-CoV-2 genomic surveillance from community-distributed rapid antigen tests
Authors: Emmen Isla E. , Vuyk William C. , Lail Andrew J. , Wolf Sydney , O’Connor Eli J. , Dalvie Rhea , Bhasin Maansi , Virdi Aanya , White Caroline , Hassan Nura R. , Richardson Alex , VanSleet Grace , Weiler Andrea , Rounds-Dunn Savannah , Van Horn Kenneth , Gartler Marc , Jorgenson Jane , Spelman Michael , Ottosen Sean , Minor Nicholas R. , Wilson Nancy , Friedrich Thomas C. , O’Connor David H.
Published: August 2024

In the United States, SARS-CoV-2 genomic surveillance initially relied almost entirely on residual diagnostic specimens from nucleic acid amplification-based tests (NAATs). The use of NAATs waned after the end of the COVID-19 Public Health Emergency. We partnered with local- and state-level public health agencies and the Dane County Public Library System to continue genomic surveillance by obtaining SARS-CoV-2 genome sequences from freely available community rapid antigen tests (RATs). From August 15, 2023 to February 29, 2024 we received 227 tests, from which we generated 127 sequences with >10x depth of coverage for ≥90% of the genome. In a subset of tests, lower Ct values correlated with sequence success. Our results demonstrate that collecting and sequencing from RATs in partnership with community sites is a practical approach for sustaining SARS-CoV-2 genomic surveillance.
Multicellular, fluid flow-inclusive hepaticin vitromodels using NANOSTACKSTM: a human-relevant model for drug response prediction
Authors: Talari Abdullah , Sbordoni Raffaello , Hoti Valmira , Patel Imran I. , Martin Francis L. , Raza Ahtasham , Llabjani Valon
Published: August 2024

Drug-induced liver injury (DILI) continues to be the leading cause of drug attrition during clinical trials as well as the number one cause of post-market drug withdrawal due to the limited predictive accuracy of preclinical animal and conventionalin vitromodels. In this study, the NANOSTACKSTMplatform was introduced as a novelin vitrotool to buildin vivo-relevant organ models for predicting drug responses. In particular, hepatic models including monocultures of primary human hepatocytes (PHH), tricultures of PHH, human stellate cells (HSC) and human liver endothelial cells (LECs), and tetracultures of PHH, HSC, LECs and human Kupffer cells (KC) were developed under static and fluid flow-inclusive conditions. All hepatic models were characterised by assessing albumin, urea, CYP3A4 and ATP production. In addition, the preclinical DILI screening potential of the fluid flow-inclusive monoculture and triculture models were assessed by testing the hepatotoxicity of Zileuton, Buspirone and Cyclophosphamide. NANOSTACKS™ represents a promising tool for the development of complexin vitromodels.
Orthopoxvirus-specific antibodies wane to undetectable levels one year after MVA-BN vaccination of at-risk individuals
Authors: van Leeuwen Leanne P. M. , Shamier Marc C. , Verstrepen Babs E. , Götz Hannelore M. , Schmitz Katharina S. , Akhiyate Najlae , Wijnans Koen , Bogers Susanne , van Royen Martin E. , van Gorp Eric C. M. , Koopmans Marion P. G. , de Vries Rory D. , GeurtsvanKessel Corine H. , Zaeck Luca M.
Published: August 2024

In response to the 2022-2023 mpox outbreak, widespread vaccination with modified vaccinia Ankara-Bavarian Nordic was initiated. Here, we demonstrate that orthopoxvirus-specific binding and MVA-neutralizing antibodies wane to undetectable levels one year post-vaccination in at-risk individuals without pre-existing immunity. Continuous surveillance is essential to understand the impact of declining antibody levels.
Fasting, ketogenic and anti-inflammatory diets stabilized active relapsing-remitting multiple sclerosis over 18 months – a randomized, controlled study
Authors: Bahr Lina S. , Bellmann-Strobl Judith , Koppold Daniela A. , Rust Rebekka , Schmitz-Hübsch Tanja , Olszewska Maja , Stadlbauer Jean , Bock Markus , Scheel Michael , Chien Claudia , Multmeier Jan , Krannich Alexander , Michalsen Andreas , Paul Friedemann , Mähler Anja
Published: August 2024

Background

Multiple sclerosis (MS) is the most common inflammatory disease of the central nervous system in young adulthood leading to disability and early retirement. Ketone-based diets improve the disease course in MS animal models and health outcomes in different pilot studies of neurodegenerative diseases.

Methods

We enrolled 105 individuals with relapsing-remitting MS (RRMS) in an 18-month, randomized, controlled study, and randomized them into 1) standard healthy diet (SD) as recommended by the German Nutrition Society, 2) fasting diet (FD) with 7-day fasts every 6 months with intermittent fasting at 6 of 7 days a week or 3) ketogenic diet (KD) with 20-40 g carbohydrates per day. Primary outcome was the number of new MRI lesions after 18 months in the KD and FD compared to SD and compared to baseline. Secondary outcomes included further MRI outcomes, disease biomarkers as well as metabolic, and clinical MS outcomes.

Results

Eighty-one participants completed the study. The primary endpoint number of new T2 lesions after 18 months did not change in any of the groups (SD 0 (0-(−1)), FD 0 (2-0), KD 0 (2-0)). Compared to baseline, in the FD group, Neurofilament light chain (NfL) - concentrations were lower at 9 months (−1.94 pg/mL, p = 0.042) and depressive symptoms improved slightly at 18 months (p = 0.079). In the KD group, cognition improved at 18 months (symbol digit modalities test +3.7, p = 0.020). Cardiometabolic risk markers (body mass index, abdominal fat, blood lipids, adipokines, blood pressure) improved in all three groups at 9 months differently and were partially associated with clinical outcomes in the FD and KD group.

Conclusion

Dietary interventions may stabilize RRMS disease course and improve cardiometabolic risk factors, cognition, and depressive symptoms, providing valuable complementary treatment options.

Trial registration

ClinicalTrials.gov,NCT03508414. Retrospectively registered on 25 April 2018.
Protection from Killed Whole-Cell Cholera Vaccines: A Systematic Review and Meta-Analysis
Authors: Xu Hanmeng , Tiffany Amanda , Luquero Francisco , Kanungo Suman , Bwire Godfrey , Qadri Firdausi , Garone Daniela , Ivers Louise C , Lee Elizabeth C , Malembaka Espoir Bwenge , Mendibourne Vincent , Bouhenia Malika , Breakwell Lucy , Azman Andrew S
Published: August 2024

Background

Killed whole-cell oral cholera vaccines (kOCVs) are a standard prevention and control measure in cholera endemic areas, outbreaks, and humanitarian emergencies. Recently, new evidence has emerged and the ways in which the vaccines are used have changed. An updated synthesis of evidence on kOCV protection, is needed.

Methods

We systematically searched for randomized trials and observational studies that reported estimates of protection against confirmed cholera conferred by kOCVs. Eligible studies in English, French, Spanish or Chinese published through March 8, 2024, were included. Data on efficacy and effectiveness were extracted as were the number of doses, duration of follow-up, and age group. Efficacy and effectiveness estimates were summarized separately using random effects models to estimate protection by time since vaccination; meta-regression models were used to estimate protection, by dose, as a function of time since vaccination.

Findings

Twenty-three publications from five randomized controlled trials and ten observational studies were included. Average two-dose efficacy one-year post-vaccination was 55% (95%CI: 46-62%), declining to 44% (95%CI: 25-59%) four years post-vaccination. Average two-dose effectiveness was 69% (95%CI: 58-78%) one-year post-vaccination declining to 47% (95%CI: 9-70%) four years post-vaccination. Only one randomized trial assessed one-dose efficacy and found sustained protection for two years (52%; 95%CI 8-75%). Average one-dose effectiveness one year after vaccination was 60% (95%CI: 51-68%) and 47% (95%CI: 34-58%) after two years. Through age-group specific meta-analysis average 2-dose efficacy in children under five years old was half that of older individuals.

Interpretation

Two doses of kOCV provide protection against medically-attended cholera for at least four years post-vaccination. One-dose of kOCV provides protection for at least two years post-vaccination, but wanes faster than that of two doses. Children under five are less protected by kOCVs compared to those 5 years and older regardless of the number of doses received.

Funding

Bill and Melinda Gates Foundation
Severe acute respiratory syndrome (SARS) mathematical models and disease parameters: a systematic review and meta-analysis
Authors: Morgenstern Christian , Rawson Thomas , Routledge Isobel , Kont Mara , Imai-Eaton Natsuko , Skarp Janetta , Doohan Patrick , McCain Kelly , Johnson Rob , Unwin H. Juliette T. , Naidoo Tristan , Dee Dominic P , Parchani Kanchan , Cracknell Daniels Bethan N , Vicco Anna , Drake Kieran O. , Christen Paula , Sheppard Richard J , Leuba Sequoia I , Hicks Joseph T , McCabe Ruth , Nash Rebecca K , Santoni Cosmo N ,   Pathogen Epidemiology Review Group, Cuomo-Dannenburg Gina , van Elsland Sabine , Bhatia Sangeeta , Cori Anne
Published: August 2024

We conducted a systematic review (PROSPERO CRD42023393345) of severe acute respiratory syndrome (SARS) transmission models and parameters characterising its transmission, evolution, natural history, severity, risk factors and seroprevalence. Information was extracted using a custom database and quality assessment tool.

We extracted 519 parameters, 243 risk factors, and 112 models from 288 papers. Our analyses show SARS is characterised by high lethality (case fatality ratio 10.9%), transmissibility (R0range 1.1-4.59), and is prone to superspreading (20% top infectors causing up to 91% of infections). Infection risk was highest among healthcare workers and close contacts of infected individuals. Severe disease and death were associated with age and existing comorbidities. SARS’s natural history is poorly characterised, except for the incubation period and mean onset-to-hospitalisation.

Our associated R package, epireview, contains this database, which can continue to be updated to maintain a living review of SARS epidemiology and models, thus providing a key resource for informing response to future coronavirus outbreaks.
α-KIDS: A novel feature evaluation in the ultrahigh-dimensional right-censored setting, with application to Head and Neck Cancer
Authors: Urmi Atika FArzana , Ke Chenlu , Bandyopadhyay Dipankar
Published: August 2024

Abstract

Recent advances in sequencing technologies have allowed collection of massive genome-wide information that substantially enhances the diagnosis and prognosis of head and neck cancer. Identifying predictive markers for survival time is crucial for devising prognostic systems, and learning the underlying molecular driver of the cancer course. In this paper, we introduceα-KIDS, a model-free feature screening procedure with false discovery rate (FDR) control for ultrahigh dimensional right-censored data, which is robust against unknown censoring mechanisms. Specifically, our two-stage procedure initially selects a set of important features with a dual screening mechanism using nonparametric reproducing-kernel-based ANOVA statistics, followed by identifying a refined set (of features) under directional FDR control through a unified knockoff procedure. The finite sample properties of our method, and its novelty (in light of existing alternatives) are evaluated via simulation studies. Furthermore, we illustrate our methodology via application to a motivating right-censored head and neck (HN) cancer survival data derived from The Cancer Genome Atlas, with further validation on a similar HN cancer data from the Gene Expression Omnibus database. The methodology can be implemented via the R package DSFDRC, available in GitHub.
Clade I Mpox virus genomic diversity in the Democratic Republic of the Congo, 2018 - 2024: Predominance of Zoonotic Transmission
Authors: Kinganda-Lusamaki Eddy , Amuri-Aziza Adrienne , Fernandez Nicolas , Makangara-Cigolo Jean-Claude , Pratt Catherine , Hasivirwe Vakaniaki Emmanuel , Hoff Nicole A. , Luakanda Gradi , Akil-Bandali Prince , Sabiti Nundu Sabin , Mulopo-Mukanya Noella , Ngimba Michel , Modadra-Madakpa Brigitte , Diavita Ruth , Paku Princesse , Pukuta-Simbu Elisabeth , Merritt Sydney , O’Toole Áine , Low Nicola , Nkuba-Ndaye Antoine , Kavunga-Membo Hugo , Shongo Robert , Liesenborghs Laurens , Wawina-Bokalanga Tony , Vercauteren Koen , Mukadi-Bamuleka Daniel , Subissi Lorenzo , Muyembe Jean-Jacques , Kindrachuk Jason , Ayouba Ahidjo , Rambaut Andrew , Delaporte Eric , Tessema Sofonias , D’Ortenzio Eric , Rimoin Anne W. , Hensley Lisa E. , Mbala-Kingebeni Placide , Peeters Martine , Ahuka-Mundeke Steve
Published: August 2024

Background

Recent reports raise concerns on the changing epidemiology of mpox in the Democratic Republic of the Congo (DRC), with increasing case counts, sexual contact-mediated clusters, and sustained human-to-human transmission driven by a novel monkeypox virus (MPXV) subclade, clade Ib. However, only a limited number of clade I MPXV genomes have been characterized so far, from a limited number of regions.

Methods

We conducted whole genome sequencing of 603 mpox-positive samples that were collected from 581 patients between 2018-2024 in 17 of the 26 provinces of the DRC.

Results

Genome coverage was at least 70% for 429/603 (71.1%) samples and near full-length MPXV genomes (>90% coverage) were obtained for 348/603 (57.7%) samples from 337 patients. All newly generated MPXV sequences belonged to clade I, among which 17 were clade Ib strains, all from patients infected in 2024 in the South-Kivu province. The large majority (>95%) of the new strains fall within previously described clade Ia groups and potential new groups have also been observed. The low number of APOBEC3 mutations found among clade Ia suggests that most human mpox cases are probably linked to zoonotic transmissions. Genetically diverse MPXV lineages co-circulate in small geographic areas during the same outbreak suggesting multiple zoonotic introductions over a short period from one or multiple reservoir species. Recent identification of mpox cases in Kinshasa shows that multiple lineages circulate in a large urban center, indicating separate introduction events.

Conclusion

The mpox epidemic in the DRC exhibits two distinct patterns. In traditional endemic regions, the epidemic is predominated by zoonotic spill-over events involving clade Ia. Conversely, in the eastern part of the country, the clade Ib outbreak is driven by human-to-human transmission highlighting the need for a coordinated response effort at the national, regional and international levels.
Compound screening in primary human airway basal cells identifies Wnt pathway activators as potential pro-regenerative therapies
Authors: Ishii Yuki , Orr Jessica C. , El Mdawar Marie-Belle , de Pilger Denise R. Bairros , Pearce David R. , Lazarus Kyren A. , Graham Rebecca E. , Nikolić Marko Z. , Ketteler Robin , Carragher Neil O. , Janes Sam M. , Hynds Robert E.
Published: August 2024

Regeneration of the airway epithelium restores barrier function and mucociliary clearance following lung injury and infection. Basal cells are tissue-resident airway stem cells that enact regeneration, yet the mechanisms regulating their proliferation and differentiation remain incompletely understood. To identify compounds that promote primary human airway basal cell proliferation, we performed phenotype-based compound screening of 1,429 compounds (from the ENZO and Prestwick Chemical libraries) in 384-well format using primary cells transduced with lentiviral luciferase. 16 pro-proliferative compounds validated in independent donor cell cultures, with several hit compounds activating the Wnt signalling pathway. The effects of compounds on proliferation were further explored in concentration-response, colony formation and 3D organoid assays. Structurally and functionally-related compounds that more potently induced both Wnt activation and basal cell proliferation were investigated. One such compound, 1-azakenpaullone, induced Wnt target gene activation and basal cell proliferation in mice in the absence of tracheal injury. Our results demonstrate the pro-proliferative effect of small-molecule Wnt activators on airway basal cells. These findings contribute to the rationale to develop novel approaches to modulate Wnt signalling during airway epithelial repair.

Summary statement

Ishii, Orr and colleagues perform a high-throughput screen of 1,429 compounds in primary human airway epithelial cells, identifying Wnt activating compounds as promoters of proliferation.
Control of pili synthesis and putrescine homeostasis inEscherichia coli
Authors: Mehta Iti , Hogins Jacob , Hall Sydney , Vragel Gabrielle , Ambagaspitiye Sankalya , Zimmern Philippe , Reitzer Larry
Published: August 2024

Polyamines are biologically ubiquitous cations that bind to nucleic acids, ribosomes, and phospholipids and, thereby, modulate numerous processes, including surface motility inEscherichia coli. We characterized the metabolic pathways that contribute to polyamine-dependent control of surface motility in the commonly used strain W3110 and the transcriptome of a mutant lacking a putrescine synthetic pathway that was required for surface motility. Genetic analysis showed that surface motility required type 1 pili, the simultaneous presence of two independent putrescine anabolic pathways, and modulation by putrescine transport and catabolism. An immunological assay for FimA—the major pili subunit, reverse transcription quantitative PCR offimA, and transmission electron microscopy confirmed that pili synthesis required putrescine. Comparative RNAseq analysis of a wild type and ΔspeBmutant which exhibits impaired pili synthesis showed that the latter had fewer transcripts for pili structural genes and forfimBwhich codes for the phase variation recombinase that orients thefimoperon promoter in the ON phase, although loss ofspeBdid not affect the promoter orientation. Results from the RNAseq analysis also suggested (a) changes in transcripts for several transcription factor genes that affectfimoperon expression, (b) compensatory mechanisms for low putrescine which implies a putrescine homeostatic network, and (c) decreased transcripts of genes for oxidative energy metabolism and iron transport which a previous genetic analysis suggests may be sufficient to account for the pili defect in putrescine synthesis mutants. We conclude that pili synthesis requires putrescine and putrescine concentration is controlled by a complex homeostatic network that includes the genes of oxidative energy metabolism.
Single-Molecule Barcoding Technology for Single-Cell Genomics
Authors: Garcia-Bassets Ivan , Mo Guoya , Xia Yu , Wu Tsai-Chin , Mekuria Immanuel , Mikhaylova Veronika , Rzepka Madison , Kawamura Tetsuya , Chang Peter L. , Paasch Amber , Pham Long , Venugopal Surya Shiv , Sanchez Sandra , de Souza Janaina S. , Yao Likun , Gu Sifeng , Bodai Zsolt , Komor Alexis C. , Muotri Alysson R. , Wang Joy , Wang Yong , Lei Ming , Almenar-Queralt Angels , Chen Zhoutao
Published: August 2024

Recent advances in barcoding technologies have significantly enhanced the scalability of single-cell genomic experiments. However, large-scale experiments are still rare due to high costs, complex logistics, and laborintensive procedures. To facilitate the routine application of the largest scalability, it is critical to simplify the production and use of barcoding reagents. Here, we introduce AmpliDrop, a technology that initiates the barcoding process using a pool of inexpensive single-copy barcodes and integrates barcode multiplicity generation with tagging of cellular content into a single reaction driven by DNA polymerase during library preparation. The barcoding reactions are compartmentalized using an electronic pipette or a robotic or standalone liquid handling system. These innovations eliminate the need for barcoded beads and complex combinatorial indexing workflows and provide flexibility for a wide range of scales and tube formats, as well as compatibility with automation. We show that AmpliDrop is capable of capturing transcriptomes and chromatin accessibility, and it can also be adapted for user-customized applications, including antibody-based protein detection, bacterial or viral DNA detection, and CRISPR perturbations without dual guide RNA-expression vectors. We validated AmpliDrop by investigating the influence of short-term static culturing on cell composition in human forebrain organoids, revealing metabolic reprogramming in lineage progenitors.
Dual quorum-sensing control of purine biosynthesis drives pathogenic fitness ofEnterococcus faecalis
Authors: Zlitni Soumaya , Bowden Sierra , Sberro Hila , Torres Marcelo D. T. , Vaughan Joan M , Pinto Antonio F M , Pinto Yishay , Fernandez Daniel , Röst Hannes , Saghatelian Alan , de la Fuente-Nunez Cesar , Bhatt Ami S.
Published: August 2024

Enterococcus faecalisis a resident of the human gut, though upon translocation to the blood or body tissues, it can be pathogenic. Here we discover and characterize two peptide-based quorum-sensing systems that transcriptionally modulate de novo purine biosynthesis inE. faecalis. Using a comparative genomic analysis, we find that most enterococcal species do not encode this system;E. moraviensis,E. haemoperoxidusandE. caccae, three species that are closely related toE. faecalis, encode one of the two systems, and onlyE. faecalisencodes both systems. We show that these systems are important for the intracellular survival ofE. faecaliswithin macrophages and for the fitness ofE. faecalisin a murine wound infection model. Taken together, we combine comparative genomics, microbiological, bacterial genetics, transcriptomics, targeted proteomics and animal model experiments to describe a paired quorum sensing mechanism that directly influences central metabolism and impacts the pathogenicity ofE. faecalis.
Quantitative and Kinetic Proteomics Reveal ApoE Isoform-dependent Proteostasis Adaptations in Mouse Brain
Authors: Zuniga Nathan R. , Earls Noah E. , Denos Ariel E. A. , Elison Jared M. , Jones Benjamin S. , Smith Ethan G. , Moran Noah G. , Brown Katie L. , Romero Gerome M. , Hyer Chad D. , Wagstaff Kimberly B. , Almughamsi Haifa M. , Transtrum Mark K. , Price John C.
Published: August 2024

Apolipoprotein E (ApoE) polymorphisms modify the risk of neurodegenerative disease with the ApoE4 isoform increasing and ApoE2 isoform decreasing risk relative to the ‘wild-type control’ ApoE3 isoform. To elucidate how ApoE isoforms alter the proteome, we measured relative protein abundance and turnover in transgenic mice expressing a human ApoE gene (isoform 2, 3, or 4). This data provides insight into how ApoE isoforms affect thein vivosynthesis and degradation of a wide variety of proteins. We identified 4849 proteins and tested for ApoE isoform-dependent changes in the homeostatic regulation of ∼2700 ontologies. In the brain, we found that ApoE4 and ApoE2 both lead to modified regulation of mitochondrial membrane proteins relative to the wild-type control ApoE3. In ApoE4 mice, this regulation is not cohesive suggesting that aerobic respiration is impacted by proteasomal and autophagic dysregulation. ApoE2 mice exhibited a matching change in mitochondrial matrix proteins and the membrane which suggests coordinated maintenance of the entire organelle. In the liver, we did not observe these changes suggesting that the ApoE-effect on proteostasis is amplified in the brain relative to other tissues. Our findings underscore the utility of combining protein abundance and turnover rates to decipher proteome regulatory mechanisms and their potential role in biology.

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