bluuebunny/crossref_metadata_2025 huggingface dataset:
Adjunctive use of hypnosis for clinical pain: a systematic review and meta-analysis
Authors: Jones Hannah G. , Rizzo Rodrigo R. N. , Pulling Brian W. , Braithwaite Felicity A. , Grant Ashley R. , McAuley James H. , Jensen Mark P. , Moseley G. Lorimer , Rees Amy , Stanton Tasha R.
Published: September 2024

Systematic reviews suggest that stand-alone hypnotic suggestions may improve pain outcomes compared with no treatment, waitlist, or usual care. However, in clinical practice, hypnosis is often provided adjunctively with other interventions, which might have different effects than those reported in previous reviews. This systematic review aimed to summarize the analgesic effects of adjunctive hypnosis in adults with clinical pain. Seven databases (MEDLINE, Embase, PsycINFO, Emcare, SCOPUS, CENTRAL, Cochrane) were searched up to January 2024. Randomised controlled trials comparing the analgesic effects of adjunctive hypnosis (hypnosis + primary intervention) with those of the primary intervention alone were included. Meta-analyses (random-effects model) calculated mean differences (MD, [95% confidence intervals]) for pain intensity (0–100). Seventy studies were pooled in meta-analyses (n = 6078). Hypnosis adjunctive to usual care had a small additional analgesic effect (chronic pain: −8.2 [−11.8, −1.9]; medical procedures/surgical pain: −6.9 [−10.4, −3.3]; burn wound care: −8.8 [−13.8, −3.9]). Hypnosis adjunctive to education had a medium additional analgesic effect for chronic pain (−11.5 [−19.7, 3.3]) but not postsurgery pain (−2.0 [−7.8, 3.7]). When paired with psychological interventions, hypnosis slightly increased analgesia in chronic pain only at the three-month follow-up (−2 [−3.7, −0.3]). Hypnosis adjunctive to medicines had a medium additional analgesic effect for chronic pain (−13.2, [−22.5, −3.8]). The overall evidence certainty is very low; therefore, there is still uncertainty about the analgesic effects of adjunctive hypnosis. However, hypnosis adjunct to education may reduce pain intensity for chronic pain. Clarification of proposed therapeutic targets of adjunctive hypnosis to evaluate underlying mechanisms is warranted.
The effects of spinal stabilization exercises on functional exercise capacity in individuals with transtibial amputation: A randomized trial
Authors: Çerezci-Duygu Senay , Erbahçeci Fatih , Durutürk Neslihan , Ümit-Yemişçi Oya
Published: September 2024

Background:

Optimization of mobility activities with spinal stabilization exercises and reducing spinal loads in individuals with transtibial amputation are recommended by researchers; however, the effect of spinal stabilization exercises on functional exercise capacity has not been investigated.

Objective:

This study aims to investigate the effect of spinal stabilisation exercises on functional exercise capacity in individuals with transtibial amputation.

Study Design:

Randomized controlled trial with concealed allocation, assessor blinding.

Methods:

Eighteen individuals with transtibial amputation were included. Conventional physiotherapy program was applied to individuals in control group, and spinal stabilization exercise training was applied to individuals in intervention group together with conventional physiotherapy program for 8 weeks. The primary outcome was maximal oxygen uptake during 6-Minute Stepper Test. The secondary outcomes were maximal energy expenditure, step count and fatigue during 6-Minute Stepper Test, perceived mobility level with prosthesis, and stabilization strength of deep spinal muscles.

Results:

In the within-group comparisons, the change in the functional exercise capacity, step count, and stabilization strength of deep spinal muscles were found to be statistically significant in both groups. In the between-group comparison, the changes in the functional exercise capacity, perceived mobility level, and stabilization strength of deep spinal muscles were found to be significant in favor of the group in which spinal stabilization exercises were applied.

Conclusions:

Along with improvement in proximal control of movement, improvements were observed in some parameters that are indicative of physical capacity. Considering the described developments, exercise programs focused on spinal stabilization in individuals with amputation are becoming a serious alternative in clinical practice.
The evolution of knowledge for treating Gram-negative bacterial infections
Authors: Burillo Almudena , Bouza Emilio
Published: September 2024

Purpose of review

Infections caused by nonprimarily pathogenic Gram-negative bacilli (GNB) have been increasingly reported from the second half of the 20th century to the present. This phenomenon has expanded during the antibiotic era and in the presence of immunodeficiency.

Before the discovery of sulphonamides and penicillin G, infections caused by GNB were rare compared to Gram-positive infections. The advent of anticancer therapy, the expansion of surgical procedures, the use of corticosteroids, and the implantation of prosthetic materials, along with better control of Gram-positive infections, have promoted the current increase in GNB infections.

GNB have similar antimicrobial targets to Gram-positive bacteria. However, only antibiotics that can penetrate the double membrane of GNB and remain in them for a sufficient duration have antibacterial activity against them.

Recent findings

Sulphonamides and early penicillins had limited activity against GNB. Ampicillin and subsequent beta-lactams expanded their spectrum to treat GNB. Aminoglycosides may re-surge with less toxic drugs, as highly resistant to beta-lactams GNB rise. Polymyxins, tetracyclines, and fluoroquinolones are also used for GNB. Combinations with other agents may be needed in specific cases, such as in the central nervous system and prostate, where beta-lactams may have difficulty reaching the infection site.

Alternatives to current treatments must be sought in the discovery of new drug families and therapies such as phage therapy combined with antibiotics.

Narrower-spectrum immunosuppressive therapies and antibiotics, antimicrobials that minimally intervene with the human microbiota, and instant diagnostic methods are necessary to imagine a future where currently dominant bacteria in infectious pathology lose their preeminence.
Update on diagnosis and treatment of fungal meningitis: lessons from recent outbreaks
Authors: Beltran-Reyes Paula , Ostrosky-Zeichner Luis , Gonzalez-Lara Maria F.
Published: September 2024

Purpose of review

Recently, fungal meningitis outbreaks have occurred in association with neuraxial and epidural anesthesia in immunocompetent patients. Herein, we describe the course of those outbreaks, their diagnosis, treatment, prognosis, and lessons learned.

Recent findings

Two outbreaks of Fusarium solani meningitis during 2022–2023 were associated with epidural anesthesia in two distant cities in Mexico (Durango and Matamoros). The initial etiological agent identification was delayed due to insensitivity of cultures. A Fusarium solani qPCR was validated and positive in 38% cerebrospinal fluid (CSF) samples from Durango, while BD-Glucan allowed early diagnosis of the index case in Matamoros. Antifungal treatment with voriconazole and liposomal amphotericin B (L-AmB) was recommended. Overall mortality was 51%. Once the cause was confirmed, some patients received fosmanogepix.

Fungal meningitis outbreaks due to filamentous fungi are usually associated with direct epidural inoculation. They result in severe presentations and high mortality. Early diagnosis should be suspected, BD-Glucan CSF testing screening is recommended. Aggressive antifungal treatment based on antifungal susceptibility testing should be administered as early as possible. The advent of molecular diagnostic methods and new antifungal drugs may allow for timely diagnosis and treatment, increasing the chances of survival.
Updates for newly diagnosed and recurrent glioblastoma: a review of recent clinical trials
Authors: Fukushima Corinna M. , de Groot John
Published: September 2024

Purpose of review

Glioblastoma (GBM) is the most common and devastating primary malignant brain tumor. We summarize recent advances in radiotherapy, immunotherapy, and targeted therapy approaches for the treatment of newly diagnosed and recurrent glioblastoma. We also introduce ongoing clinical trials.

Recent findings

Recent clinical trials have explored multiple novel strategies to treat GBM including the use of oncoviruses, chimeric antigen receptor (CAR) T cell therapy, vaccines, radiotherapy, and novel drug delivery techniques to improves drug penetrance across the blood brain barrier. Approaches to improve drug delivery to brain tumors have the potential to expand treatment options of existing therapies that otherwise have poor brain tumor penetrance. Immunotherapy has been of keen interest in both newly diagnosed and recurrent glioblastoma. Vaccines SurVaxM and DCVax-L have shown initial promise in phase II and III trials, respectively. CAR T cell therapy trials are in their early phases but hold promise in both newly diagnosed and recurrent glioblastoma.

Although progress to improve outcomes for GBM patients has been modest, multiple novel strategies utilizing combination therapies, focused ultrasound to improve drug delivery, and novel immunotherapies are underway.
Elucidating nanostructural organization and photonic properties of butterfly wing scales using hyperspectral microscopy
Authors: Jessop Anna-Lee , Pirih Primož , Wang Limin , Patel Nipam H. , Clode Peta L. , Schröder-Turk Gerd E. , Wilts Bodo D.
Published: September 2024

Biophotonic nanostructures in butterfly wing scales remain fascinating examples of biological functional materials, with intriguing open questions with regard to formation and evolutionary function. One particularly interesting butterfly species,
Erora opisena
(Lycaenidae: Theclinae), develops wing scales that contain three-dimensional photonic crystals that closely resemble a single gyroid geometry. Unlike most other gyroid-forming butterflies,
E. opisena
develops discrete gyroid crystallites with a pronounced size gradient hinting at a developmental sequence frozen in time. Here, we present a novel application of a hyperspectral (wavelength-resolved) microscopy technique to investigate the ultrastructural organization of these gyroid crystallites in dry, adult wing scales. We show that reflectance corresponds to crystallite size, where larger crystallites reflect green wavelengths more intensely; this relationship could be used to infer size from the optical signal. We further successfully resolve the red-shifted reflectance signal from wing scales immersed in refractive index liquids with varying refractive index, including values similar to water or cytosol. Such photonic crystals with lower refractive index contrast may be similar to the hypothesized nanostructural forms in the developing butterfly scales. The ability to resolve these fainter signals hints at the potential of this facile light microscopy method for
in vivo
analysis of nanostructure formation in developing butterflies.
Modelling SARS-CoV-2 infection in a human alveolus microphysiological system
Authors: Šuligoj Tanja , Coombes Naomi S. , Booth Catherine , Savva George M. , Bewley Kevin R. , Funnell Simon G.P. , Juge Nathalie
Published: September 2024

The coronavirus 2019 pandemic has highlighted the importance of physiologically relevant in vitro models to assist preclinical research. Here, we describe the adaptation of a human alveolus microphysiological system (MPS) model consisting of primary human alveolar epithelial and lung microvascular endothelial cells to study infection with SARS-CoV-2 at Biosafety Level 3 facility. This infection model recapitulates breathing-like stretch and culture of epithelial cells at the air–liquid interface and resulted in clinically relevant cytopathic effects including cell rounding of alveolar type 2 cells and disruption of the tight junction protein occludin. Viral replication was confirmed by immunocytochemical nucleocapsid staining in the epithelium and increased shedding of SARS-CoV-2 virus within 2 days post-infection, associated with changes in innate host immune responses. Together, these data demonstrate that, under the experimental conditions used in this work, this human alveolus MPS chip can successfully model SARS-CoV-2 infection of human alveolar lung cells.
Peribacillus simplex and Klebsiella pneumoniae Responsible for Pyonephrosis with Secondary Psoas Abscess: A Case Report
Authors: Malihy Zakaria , Abassor Tilila , Benlahlou Yassine , Benaissa Elmostafa , Chadli Mariama
Published: September 2024

Bacterial urinary tract infections (UTIs) are common, ranging from benign cystitis to complicated pyelonephritis, which can lead to severe complications such as pyonephrosis and sepsis. Pyonephrosis, characterized by the presence of pus in the renal cavities, often requires urgent urological intervention. We report a unique case of pyonephrosis with a psoas abscess caused by Klebsiella pneumoniae (K. pneumoniae) and Peribacillus simplex (P. simplex) in a 64-year-old diabetic female patient. This is the first case of pyonephrosis caused by P. simplex. The patient presented with acute right lumbar pain, fever, and altered consciousness. Imaging revealed severe right hydronephrosis, pyonephrosis, and a perirenal phlegmon infiltrating the psoas with abscesses. Surgical drainage and nephrectomy were performed. Microbiological and proteomic analysis identified K. pneumoniae and P. simplex.This case highlights the importance of considering environmental bacteria like P. simplex in severe infections and ensuring rigorous protocols to avoid contamination. Successful management of pyonephrosis relies on prompt surgical drainage and appropriate antibiotic therapy based on culture results.
Potent and selective repression ofSCN9Aby engineered zinc finger repressors for the treatment of neuropathic pain
Authors: Samie Mohammad , Parman Toufan , Jalan Mihika , Lee Jisoo , Dunn Patrick , Eshleman Jason , Vidales Dianna Baldwin , Holter Josh , Jones Brian , Pan Yonghua , Falaleeva Marina , Hinkley Sarah , Goodwin Alicia , Chen Tammy , Bhardwaj Sumita , Ward Alex , Trias Michael , Chikere Anthony , Som Madhura , Lu Yanmei , Yadav Sandeep , Meyer Kathleen , Zeitler Bryan , Fontenot Jason , Pooler Amy
Published: September 2024

Peripheral neuropathies are estimated to affect several million patients in the US with no long-lasting therapy currently available. In humans, the Nav1.7 sodium channel, encoded by theSCN9Agene, is involved in a spectrum of inherited neuropathies, and has emerged as a promising target for analgesic drug development. The development of a selective Nav1.7 inhibitor has been challenging, in part due to structural similarities among other Nav channels. Here we present preclinical studies for the first genomic medicine approach using engineered zinc finger repressors (ZFRs) specifically targeting human/nonhuman primate (NHP)SCN9A. AAV-mediated delivery of ZFRs in human iPSC-derived neurons resulted in 90% reduction ofSCN9Awith no detectable off-target activity. To establish proof-of-concept, a ZFR targeting the mouseScn9awas assessed in the SNI neuropathic pain mouse model, which resulted in up to 70% repression ofScn9ain mouse DRGs and was associated with reduction in pain hypersensitivity as measured by increased mechanical- and cold-induced pain thresholds. AAV-mediated intrathecal delivery of ZFR in NHPs demonstrated up to 60% repression ofSCN9Ain bulk DRG tissue and on single-cell levels in the nociceptors. The treatment was well tolerated in NHPs, and no dose-limiting findings were observed four weeks after a single intrathecal injection. Taken together, our results demonstrate that AAV-delivered ZFR targeting theSCN9Agene is promising and supports further development as a potential therapy for peripheral neuropathies.
Herbivore prevalence poorly predicts yield in diverse cropping systems
Authors: Croijmans Luuk , Mertens Daan , van Apeldoorn Dirk F. , Jia Yufei , Hernández Nelson Ríos , Poelman Erik H.
Published: September 2024

Industrialized agriculture needs sustainable alternatives to pesticides to avoid negative impacts on the environment and human health. Crop diversification is known to decrease pest pressure in agricultural crops. Up till now, effects of insect herbivores on crop yield are often assumed equal among cropping systems. Here, we show that cropping system alters the effect that herbivores have on cabbage crop yield, where more herbivores do not necessarily lead to reduced yields. Our most diverse cropping system had simultaneously the highest number of herbivores and highest crop yield. Conversely, in a cultivar mixture we observed negative impacts of herbivores on yield. Our study shows that, in addition to the time of arrival and type of herbivore, cropping system should be considered when assessing how insect herbivores affect crop yield. We emphasize how our perception of herbivorous insects as pests is flawed and limits conservation efforts and sustainable farming practices.
AlphaFold2 SLiM screen for LC3-LIR interactions in autophagy
Authors: Stuke Jan F. M. , Hummer Gerhard
Published: September 2024

In selective autophagy, cargo recruitment is mediated by LC3-interacting regions (LIRs) / Atg8-interacting motifs (AIMs) in the cargo or cargo receptor proteins. The binding of these motifs to LC3/Atg8 proteins at the phagophore membrane is often modulated by post-translational modifications, especially phosphorylation. As a challenge for computational LIR predictions, sequences may contain the short canonical (W/F/Y)XX(L/I/V) motif without being functional. Conversely, LIRs may be formed by non-canonical but functional sequence motifs. AlphaFold2 has proven to be useful for LIR predictions, even if some LIRs are missed and proteins with thousands of residues reach the limits of computational feasibility. We present a fragment-based approach to address these limitations. We find that fragment length and phosphomimetic mutations modulate the interactions predicted by AlphaFold2. Systematic fragment screening for a range of target proteins yields structural models for interactions that AlphaFold2 and AlphaFold3 fail to predict for full-length targets. We provide guidance on fragment choice, sequence tuning, and LC3 isoform effects for optimal LIR screens. Finally, we also test the transferability of this general framework to SUMO-SIM interactions, another type of protein-protein interaction involving short linear motifs (SLiMs).
A bioengineered model of human placental exposure to environmental metals during pregnancy
Authors: Fattahi Pouria , Younesi Mousa , Lee Won Dong , Whang Keumrai , Kang Taewook , Rabinowitz Joshua D. , Aleksunes Lauren M. , Huh Dan Dongeun
Published: September 2024

Exposure of pregnant women to toxic metals is an environmental health issue associated with various pregnancy complications. Efforts to advance our biological understanding of this problem and mitigate its adverse effects, however, have been challenged by ethical concerns of human subject research during pregnancy. Here, we present an alternative approach that leverages the design flexibility, controllability, and scalability of bioengineered human reproductive tissues to enable experimental simulation and in-depth investigation of placental exposure to environmental metals in maternal circulation. Central to this method is an in vitro analog of the maternal-fetal interface and its dynamic tissue-specific environment constructed using primary human placental cells grown in a micro-engineered device. Using cadmium as a representative toxicant, we demonstrate the proof-of-concept of emulating the human placental barrier subjected to the flow of cadmium-containing maternal blood to show how this model can be used to examine adverse biological responses and impaired tissue function on both the maternal and fetal sides. Moreover, we present a mechanistic study of maternal-to-fetal cadmium transport in this system to reveal that efflux membrane transporters expressed by trophoblasts may play an important protective role against cadmium-induced toxicity. Finally, we describe metabolomic analysis of our microphysiological system to demonstrate the feasibility of discovering metabolic biomarkers that may potentially be useful for detection and monitoring of cadmium-induced placental dysfunction.
KIF5A regulates axonal repair and time-dependent axonal transport of SFPQ granules and mitochondria in human motor neurons
Authors: Guerra San Juan Irune , Brunner Jessie , Eggan Kevin , Toonen Ruud F. , Verhage Matthijs
Published: September 2024

Mutations in the microtubule binding motor protein, kinesin family member 5A (KIF5A), cause the fatal motor neuron disease, Amyotrophic Lateral Sclerosis. While KIF5 family members transport a variety of cargos along axons, it is still unclear which cargos are affected byKIF5Amutations. We generatedKIF5Anull mutant human motor neurons to investigate the impact of KIF5A loss on the transport of various cargoes and its effect on motor neuron function at two different timepointsin vitro. The absence of KIF5A resulted in reduced neurite complexity in young motor neurons (DIV14) and significant defects in axonal regeneration capacity at all developmental stages. KIF5A loss did not affect neurofilament transport but resulted in decreased mitochondria motility and anterograde speed at DIV42. More prominently, KIF5A depletion strongly reduced anterograde transport of SFPQ-associated RNA granules in DIV42 motor neuron axons. We conclude that KIF5A most prominently functions in human motor neurons to promote axonal regrowth after injury as well as to anterogradely transport mitochondria and, to a larger extent, SFPQ-associated RNA granules in a time-dependent manner.
Early NK-cell and T-cell dysfunction marks progression to severe dengue in patients with obesity and healthy weight
Authors: Gregorova Michaela , Santopaolo Marianna , Garner Lucy C. , Diamond Divya , Ramamurthy Narayan , Vi Tran Thuy , Nguyen Nguyet Minh , Vuong Nguyen Lam , Jones Eben , Nsubuga Mike , Luscombe Curtis , Thi My Hoa Vo , Chanh Ho Quang , Xuan Chau Nguyen Thi , Hoai Tam Dong Thi , Thi Le Duyen Huynh , Tam Cao Thi , Klenerman Paul , Yacoub Sophie , Rivino Laura
Published: September 2024

Dengue is a mosquito-borne virus infection affecting half of the world’s population for which therapies are lacking. The role of T and NK-cells in protection/immunopathogenesis remains unclear for dengue. We performed a longitudinal phenotypic, functional and transcriptional analyses of T and NK-cells in 124 dengue patients using flow cytometry and single-cell RNA-sequencing. We show that T/NK-cell signatures early in infection discriminate patients who will progress to severe dengue (SD) from those who do not. In patients with overweight/obesity these signatures are exacerbated compared to healthy weight patients, supporting their increased susceptibility to SD. In SD, CD4+/CD8+T-cells and NK-cells display increased co-inhibitory receptor expression and decreased cytotoxic capacity compared to non-SD. Furthermore, type-I Interferon signalling is downregulated in SD, suggesting defective virus-sensing mechanisms may underlie NK/T-cell dysfunction. We propose that dysfunctional “professional killer” T/NK-cells underpin dengue pathogenesis. Our findings pave the way for the evaluation of immunomodulatory therapies for dengue.
Death in the taste bud: engulfment of dying taste receptor cells by glial-like Type I cells
Authors: Wilson Courtney E. , Lasher Robert S. , Salcedo Ernesto , Yang Ruibiao , Dzowo Yannick , Kinnamon John C. , Finger Thomas E.
Published: September 2024

Taste buds comprise 50-100 epithelial derived cells, including glial-like cells (Type I) and two types of receptor cells (Types II and III). All of these taste cells are renewed throughout the life of an organism from a pool of uncommitted basal cells. Immature cells enter the bud at its base, maturing into one of the three mature cell types. How taste cells die and/or exit the bud, as well as the role of the glial-like cells in this process, remains unclear. Here we present morphological data obtained through Serial Blockface Scanning Electron Microscopy of murine circumvallate taste buds, revealing taste cells at the end of their life. Cells we identify as dying share morpholowgical features typical of apoptosis: swollen endoplasmic reticulum, large lysosomes, degrading organelles, distended outer nuclear membranes, heterochromatin reorganization, cell shrinkage, and cell and/or nuclear fragmentation. Most early stage dying cells have Type II cell morphologies, while a few display Type III cell features. Many dying cells maintain contacts with nerve fibers, but those postsynaptic fibers often appear to be detached from the main trunk of an afferent nerve. Dying cells, like mature Type II and III taste cells, are surrounded by glial-like Type I cells. In many instances Type I cells appear to be engulfing their dying neighbors, suggesting for them a novel, phagocytic role. Surprisingly, virtually no Type I cells display features of apoptosis, although they reportedly have the shortest residence time in taste buds. The ultimate fate of Type I cells therefore remains unknown.

Table of Contents Entry

Main Points

Dying taste cells display morphologies consistent with apoptosis.

Glial-like Type I cells engulf dying neighbors, perhaps acting as “undertakers.”

We find no dying Type I cells—all early dying cells are taste transducing Type II or III cells.
Integrating co-design into formative research for a SBCC entry-point platform for nutrition-sensitive social protection programs in low -and middle-income country settings
Authors: Turk T , Paul R , Safdar NF , Shah N , Alam SM , Choudhury SR , Shafique K , Ahmer Z , Wenndt AJ , Babar HK , Sadaf T , Bipul M
Published: September 2024

Background

Achieving adequate nutrition for vulnerable populations is an objective of the Sustainable Development Goals. Nutrition-sensitive social protection programs, including those that promote nutrition through Social and Behaviour Change Communication (SBCC), have the potential to reduce malnutrition and provide social supports to those most in need. Country-level needs assessments can clarify key issues. When supported by co-design approaches, program formative research may provide more culturally contextualised SBCC for the improved delivery of nutrition social protection to vulnerable groups. This formative study from Pakistan and Bangladesh, integrated co-design to more fully explore program beneficiary knowledge, attitudes and perceptions toward nutrition social protection to inform the design of SBCC key messages and an entry-point platform to ensure effective message dissemination.

Methods

Qualitative formative research was conducted to support findings from a systematic review. Thirty semi-structured interviews with program stakeholders and 12 focus group discussions (134 participants) were conducted with program beneficiaries in Bangladesh and Pakistan. Co-design sessions supplemented the needs assessment protocol. A COREQ checklist ensured best practice approaches in research design, analysis and reporting. NVIVO 2023 qualitative software supported the thematic analysis.

Results

Four organising themes were identified: 1. Barriers to Program Engagement, 2. Opportunities for Program Improvement, 3. Knowledge Attitudes and Practices, and 4. Target Groups, Messaging and SBCC Entry-Points, with 21 sub-themes emerging under the four organising themes. Main barriers related to resource constraints and maladministration of SPPs while opportunities identified greater integration of cash transfers with nutritious food provision, increased engagement with key influencers in vulnerable communities, and identification of culturally nuanced messages with dissemination through preferred channels. Integrating co-design sessions provided greater ownership, participation and engagement by program beneficiaries and more pragmatic SBCC solutions to challenges identified.

Conclusion

The needs assessments and integrated co-design sessions highlighted the benefits of close consultation with program beneficiaries in the design of culturally appropriate SBCC interventions to support nutrition-sensitive social protection programs. A SBCC entry-point platform was developed from participant recommendations to provide options for programmers on message designs, advocacy approaches and dissemination channels with the approaches applicable for a number of low -and middle-income countries where malnutrition is a major challenge.
SAHVER: Subarachnoid Hemorrhage Volumetric Expediting Resolution
Authors: Salman Saif , Wei Yujia , Wirtz Melina , Erickson Bradley J , Sharma Rohan , Brandmeir Nicholas , Jahromi Behnam Rezai , Miller David , Albaramony Nadia , Tawk Rabih , Freeman William David
Published: September 2024

Introduction

SubarachnoidHemorrhageVolumetricArtificialIntelligence (SAHVAI) is a novel model that segments and quantifies Subarachnoid Hemorrhage Volume (SAHV) on non-contrast CT (NCCT) scans and generates a 3D brain volumetric map called SAHVAI-3D. It is enhanced into SAHVAI-4D when measured over time. Precise measurement of SAHV is critical to future discoveryies. For example, IRRAflow is a FDA-approved ventricular irrigation and drainage system that can expedite removal of SAH blood products.

Objective

Utilize SAHVAI model to compare and quantify the course of SAHV resolution over time and generate SAHVAI-3D brain maps to help visualize significant SAHV resolution patterns and predict vasospasm.

Methods

We applied SAHVAI to SAH cases with mFS(3-4) using the NCCT scans among three groups. Group A included 1 SAH patient treated with the IRRAflow system. Group B included one SAH patient presented GCS 15 two days after ictus with no requirement for EVD. Group C included 10 patients who underwent regular EVD placement per standard of care.

Results

Group A showed expedited resolution of SAHV (1.87mL/day) with an mRS of 0 on discharge and minimal vasospasm (Figures 1, 2). Group B showed 16mL increase in SAHV suspected for aneurysmal rebleeding days (5-9), and the patient later died (mRS of 6) (Figure 3). Group C showed reduction of SAHV of ∼ 0.5ml /day (Figure 4). Further, the resultant 3D brain maps revealed that areas with the highest density of blood concentration were correlated with the severity and location of the vasospasm in all groups (Table 1).

Conclusion

SAHVAI, SAHVAI-3D and SAHVAI-4D are novel methods that reliably quantifies SAHV blood volume and changes over time including SAH blood resolution or rebleeding events. SAHVER is a model that shows how interventions such as IRRAflow can expedite SAHV resolution compared to passive EVD and non-CSF drainage groups.
Performance evaluation of an under-mattress sleep sensor versus polysomnography in≥400 nights with healthy and unhealthy sleep
Authors: Manners Jack , Kemps Eva , Lechat Bastien , Catcheside Peter , Eckert Danny , Scott Hannah
Published: September 2024

Consumer sleep trackers can provide useful insight into sleep and sleep patterns. However, large scale performance evaluation studies against direct sleep measures are needed to comprehensively understand sleep tracker accuracy. This study evaluated performance of an under-mattress sensor to estimate sleep and wake versus polysomnography, during multiple in-laboratory protocols in a large sample including individuals with and without sleep disorders and during day versus night sleep opportunities.

183 participants (51% male, mean[SD] age=45[18] years) attended the sleep laboratory for a research study that included simultaneous polysomnography and under-mattress sensor (Withings Sleep Analyzer [WSA]) recordings. Epoch-by-epoch analyses with confusion matrices were used to determine accuracy, sensitivity, and specificity of the WSA versus polysomnography. Bland-Altman plots examined bias in sleep duration, efficiency, onset-latency, and wake after sleep onset.

Overall WSA sleep-wake classification accuracy was 83%, sensitivity 95%, and specificity 37%. The WSA significantly overestimated total sleep time (48[81]minutes), Sleep efficiency (9[15]%), sleep onset latency (6[26]), and underestimated wake after sleep onset (54[78]), p<0.05. Accuracy and specificity were higher for night versus daytime sleep opportunities in healthy individuals (89% and 47% versus 82% and 26% respectively, p<0.05). Accuracy and sensitivity were also higher for healthy individuals (89% and 97%) versus those with sleep disorders (81% and 91%, p<0.05).

WSA performance is comparable to other consumer sleep trackers, with high sensitivity but poor specificity compared to polysomnography. Poorer accuracy and specificity during daytime versus night-time sleep opportunities is likely due to increased wake time and reduced sleep efficiency. Contactless, under-mattress sleep sensors show promise for accurate sleep monitoring, noting the tendency to over-estimate sleep particularly where wake time is high.
Universal coordinate on wave-shape manifold of cardiovascular waveform signal for dynamic quantification and cross-subject comparison
Authors: Lin Yu-Ting , Chou Ruey-Hsing , Wang Shen-Chih , Chang Cheng-Hsi , Wu Hau-Tieng
Published: September 2024

Objective

Quantifying physiological dynamics from nonstationary time series for clinical decision-making is challenging, especially when comparing data across different subjects. We propose a solution and validate it using two real-world surgical databases, focusing on underutilized arterial blood pressure (ABP) signals.

Method

We apply a manifold learning algorithm, Dynamic Diffusion Maps (DDMap), combined with the novel Universal Coordinate (UC) algorithm to quantify dynamics from nonstationary time series. The method is demonstrated using ABP signal and validated with liver transplant and cardiovascular surgery databases, both containing clinical outcomes. Sensitivity analyses were conducted to assess robustness and identify optimal parameters.Results:UC application is validated by significant correlations between the derived index and clinical outcomes. Sensitivity analyses confirm the algorithm’s stability and help optimize parameters.

Conclusions

DDMap combined with UC enables dynamic quantification of ABP signals and comparison across subjects. This technique repurposes typically discarded ABP signals in the operating room, with potential applications to other nonstationary biomedical signals in both hospital and homecare settings.

Clinical and Impact

The proposed manifold learning algorithm enables dynamic quantification of typically discarded ABP signals in the operation room that is comparable across subjects for clinical decision making.
Dissection of the ‘Virgin-soil’ epizootic of African swine fever in Mizoram, a Northeast state of India
Authors: Chingtham Santhalembi , Lalrohlui Freda , Remlalfakawmi Abigail , Neihthangpuii C. , Lalzoliani Esther , Roychoudhury Parimal , Subudhi Prashant Kumar , Dutta Tapan Kumar
Published: September 2024

This article aims to analyse the first-time emergence of African swine fever (ASF) in Mizoram. We collated the outbreak data and identified the time and locations of ASF emergence. To understand the impact of the outbreak, we have calculated the morbidity rate, mortality rate, case fatality rate (CFR) and overall pig depopulation rate. We identified that ASF emerged in total 178 locations in all 11 districts of Mizoram between March-July 2021, after a peak in June, and the disease continued to spread till the end of 2021 before re-emergence in March 2022. The overall morbidity rate and mortality rate of ASF between March-July 2021 in Mizoram were estimated to be 33.8% and 31.1%, while the average morbidity rate and the mortality rate of 10 districts were found to be 29.5% and 27.6% respectively. Overall CFR of ASF between March-July 2021 was estimated to be 92.1% and the average of all 11 districts was found to be 96.1%. Toward the end of 2021, the mortality rate increased by a total of 42.7% change and an average of 25.3% change. We estimated an overall 70% depopulation of susceptible pigs by disease and culling by end of 2021. This report is evidence that ASF has remained catastrophic and, keeping in view the complex nature and history of the virus on genotype adaptability associated with a high propensity for transboundary expansion, the virus continues to be a threat.
High early lactational synchrony within baboon groups predicts increased infant mortality
Authors: Winans Jack C. , Learn Niki H. , Siodi I. Long'ida , Warutere J. Kinyua , Archie Elizabeth A. , Tung Jenny , Alberts Susan C. , Markham A. Catherine
Published: September 2024

Social group composition can have fitness implications for group members by determining opportunities for affiliative and competitive interactions. Female-female competition may be particularly acute when many groupmates have young infants at the same time, with potential consequences for infant survival. Here, we used decades of data on wild baboons (Papio sp.) in Amboseli, Kenya, to examine the effects of "early lactational synchrony" (here, the proportion of females in a group with an infant <90 days old) on female-female agonistic interactions and infant survival. Because early lactation is an energetically demanding time for mothers and a risky time for infants, we expected early lactational synchrony to produce intensified competition for food and/or male protectors, resulting in more frequent female-female agonistic interactions and high infant mortality. In support of these predictions, we found that the frequency of female-female agonistic interactions increased with increasing early lactational synchrony. Reproductive state affected this relationship: while females in all states (cycling, pregnant, and postpartum amenorrhea) initiated more agonistic interactions when early lactational synchrony was high, only females in postpartum amenorrhea (including, but not limited to, females in early lactation) received more agonistic interactions. Furthermore, while high early lactational synchrony was rare, it strongly predicted infant mortality. This association may result from both aggression among adult females and infanticidal behavior by peripubertal females. These findings provide novel evidence that social dynamics may shape reproductive phenology in a nonseasonal breeder. Specifically, both competition among reproductive females and harassment from nonreproductive females may select against synchronous reproduction.
Mitochondrial genomic alterations in cholangiocarcinoma cell lines
Authors: Faipan Athitaya , Sitthirak Sirinya , Wangwiwatsin Arporn , Namwat Nisana , Klanrit Poramate , Titapan Attapol , Jareanrat Apiwat , Thanasukarn Vasin , Khuntikeo Natcha , Boulter Luke , Loilome Watcharin
Published: September 2024

Cholangiocarcinoma (CCA) is a diverse collection of malignant tumors that originate in the bile ducts. Mitochondria, the energy converters in eukaryotic cells, contain circular mitochondrial DNA (mtDNA) which has a greater mutation rate than nuclear DNA. Heteroplasmic variations in mtDNA may suggest an increased risk of cancer-related mortality, serving as a potential prognostic marker. In this study, we investigated the mtDNA variations of five CCA cell lines, including KKU- 023, KKU-055, KKU-100, KKU213A, and KKU-452 and compared them to the non-tumor cholangiocyte MMNK-1 cell line. We used Oxford Nanopore Technologies (ONT), a long-read sequencing technology capable of synthesizing the whole mitochondrial genome, which facilitates enhanced identification of complicated rearrangements in mitogenomics. The analysis revealed a high frequency of SNVs and INDELs, particularly in the D-loop,MT-RNR2,MT-CO1,MT-ND4, andMT-ND5genes. Significant mutations were detected in all CCA cell lines, with particularly notable non-synonymous SNVs such as m.8462T>C in KKU-023, m.9493G>A in KKU-055, m.9172C>A in KKU-100, m.15024G>C in KKU-213A, m.12994G>A in KKU-452, and m.13406G>A in MMNK-1, which demonstrated high pathogenicity scores. The presence of these mutations suggests the potential for mitochondrial dysfunction and CCA progression. Analysis of mtDNA structural variants (SV) revealed significant variability among the cell lines. We identified 208 SVs in KKU-023, 185 SVs in KKU-055, 231 SVs in KKU-100, 69 SVs in KKU-213A, 172 SVs in KKU-452, and 217 SVs in MMNK-1. These SVs included deletions, duplications, and inversions, with the highest variability observed in KKU-100 and the lowest in KKU-213A. Our results underscore the diverse mtDNA mutation landscape in CCA cell lines, highlighting the potential impact of these mutations on mitochondrial function and CCA cell line progression. Future research is required to investigate the functional impacts of these variants, their interactions with nuclear DNA in CCA, and their potential as targets for therapeutic intervention.

Author Summary

Bile duct cancer has the highest incidence in northeastern Thailand. In this study, we explored the mtDNA of CCA cell lines, as mitochondria play a key role in cellular energy production. We aimed to identify mutations that could serve as therapeutic targets or biomarkers. Our analysis revealed that each CCA cell line has unique mtDNA profiles, including INDELs, SVs, and SNVs such as m.8462T>C in KKU-023, m.9493G>A in KKU-055, m.9172C>A in KKU-100, m.15024G>C in KKU-213A, m.12994G>A in KKU-452, and m.13406G>A in MMNK-1, which demonstrated high pathogenicity scores. yet they also shared some common mutations. Future research is needed to understand how these mutations affect cell function, interact with nuclear DNA, and their potential for therapeutic intervention.
Enzymatic Degrading Chlorophenol Wastewater by Mixed Strains of Immobilized White Rot Fungi†
Authors: Liu Hongyuan , Lou Xueyi , Shao Yeyao , Wang Zhichao , Xiao Jiamin , Cen Kai , Chen Dingyin , Xia Qiman , Xu Wenlong , Fang Fang , Orooji Yasin , Liu Peng
Published: September 2024

To address chlorophenol wastewater pollution, immobilized mixed white rot fungi (WRF) strain microsphere was designed as a solid degradation agent, usinglignin peroxidase(LiP),manganese peroxidase(MnP), andlaccase(Lac) to degradating the wastewater. Considering the diverse physical and chemical properties of the fungal sphere, the immobilization agent formula is optimized and comprehensive environmental factor design response surface analysis are implemented to determine the delivery conditions. Consequently, the 2,4-DCP treatment rate and extracellular enzyme activity for a 1:1 encapsulation ofT. versicolorandP. sajor-cajusignificantly outperform those of individual strains. Using polyvinyl alcohol (PVA), sodium alginate (SA), and biochar as carriers, with sodium dihydrogen phosphate solution as crosslinker and SiO2/zeolite as additives, immobilizing mixed bacteria yielded a high-quality solid agent. This achieved a 99.33% 2,4-DCP degradation rate over 96 hours, with optimal dosage, pH, and initial 2,4-DCP concentration at 11.5 g/L, 5.5, and 40 mg/L. The degradation of 2,4-DCP by WRF selectively removes adjacent chlorine atoms to produce 4-CP, enhancing the dechlorination efficiency.

Graphical Abstract
The Generalizability of Cortical Area Parcellations Across Early Childhood
Authors: Tu Jiaxin Cindy , Myers Michael , Li Wei , Li Jiaqi , Wang Xintian , Dierker Donna , Day Trevor K. M. , Snyder Abraham Z. , Latham Aidan , Kenley Jeanette K. , Sobolewski Chloe M. , Wang Yu , Labonte Alyssa K. , Feczko Eric , Kardan Omid , Moore Lucille A. , Sylvester Chad M. , Fair Damien A. , Elison Jed T. , Warner Barbara B. , Barch Deanna M. , Rogers Cynthia E. , Luby Joan L. , Smyser Christopher D. , Gordon Evan M. , Laumann Timothy O. , Eggebrecht Adam T. , Wheelock Muriah D.
Published: September 2024

The cerebral cortex consists of distinct areas that develop through intrinsic embryonic patterning and postnatal experiences. Accurate parcellation of these areas in neuroimaging studies improves statistical power and cross-study comparability. Given significant brain changes in volume, microstructure, and connectivity during early life, we hypothesized that cortical areas in 1- to 3-year-olds would differ markedly from neonates and increasingly resemble adult patterns as development progresses.

Here, we parcellated the cerebral cortex into putative areas using local functional connectivity gradients in 92 toddlers at 2 years old. We demonstrate high reproducibility of these cortical regions across 1- to 3-year-olds in two independent datasets. The area boundaries in 1- to 3-year-olds were more similar to those in adults than those in neonates. While the age-specific group area parcellation better fit the underlying functional connectivity in individuals during the first 3 years, adult area parcellations might still have some utility in developmental studies, especially in children older than 6 years. Additionally, we provide connectivity-based community assignments of the parcels, showing fragmented anterior and posterior components based on the strongest connectivity, yet alignment with adult systems when weaker connectivity was included.
Deep Learning Estimation of Small Airways Disease from Inspiratory Chest CT is Associated with FEV1Decline in COPD
Authors: Chaudhary Muhammad F. A. , Awan Hira A. , Gerard Sarah E. , Bodduluri Sandeep , Comellas Alejandro P. , Barjaktarevic Igor Z. , Barr R. Graham , Cooper Christopher B. , Galban Craig J. , Han MeiLan K. , Curtis Jeffrey L. , Hansel Nadia N. , Krishnan Jerry A. , Menchaca Martha G. , Martinez Fernando J. , Ohar Jill , Vargas Buonfiglio Luis G. , Paine Robert , Bhatt Surya P. , Hoffman Eric A. , Reinhardt Joseph M.
Published: September 2024

Rationale

Quantifying functional small airways disease (fSAD) requires additional expiratory computed tomography (CT) scan, limiting clinical applicability. Artificial intelligence (AI) could enable fSAD quantification from chest CT scan at total lung capacity (TLC) alone (fSADTLC).

Objectives

To evaluate an AI model for estimating fSADTLCand study its clinical associations in chronic obstructive pulmonary disease (COPD).

Methods

We analyzed 2513 participants from the SubPopulations and InteRmediate Outcome Measures in COPD Study (SPIROMICS). Using a subset (n= 1055), we developed a generative model to produce virtual expiratory CTs for estimating fSADTLCin the remaining 1458 SPIROMICS participants. We compared fSADTLCwith dual volume, parametric response mapping fSADPRM. We investigated univariate and multivariable associations of fSADTLCwith FEV1, FEV1/FVC, six-minute walk distance (6MWD), St. George’s Respiratory Questionnaire (SGRQ), and FEV1decline. The results were validated in a subset (n= 458) from COPDGene study. Multivariable models were adjusted for age, race, sex, BMI, baseline FEV1, smoking pack years, smoking status, and percent emphysema.

Measurements and Main Results

Inspiratory fSADTLCwas highly correlated with fSADPRMin SPIROMICS (Pearson’s R = 0.895) and COPDGene (R = 0.897) cohorts. In SPIROMICS, fSADTLCwas associated with FEV1(L) (adj.β = −0.034,P< 0.001), FEV1/FVC (adj.β = −0.008,P< 0.001), SGRQ (adj.β = 0.243,P< 0.001), and FEV1decline (mL / year) (adj.β = −1.156,P< 0.001). fSADTLCwas also associated with FEV1(L) (adj.β = −0.032,P< 0.001), FEV1/FVC (adj.β = −0.007,P< 0.001), SGRQ (adj.β = 0.190,P= 0.02), and FEV1decline (mL / year) (adj.β = - 0.866,P= 0.001) in COPDGene. We found fSADTLCto be more repeatable than fSADPRMwith intraclass correlation of 0.99 (95% CI: 0.98, 0.99) vs. 0.83 (95% CI: 0.76, 0.88).

Conclusions

Inspiratory fSADTLCcaptures small airways disease as reliably as fSADPRMand is associated with FEV1decline.

Funding Source

This work was supported by NHLBI grants R01 HL142625, U01 HL089897 and U01 HL089856, by NIH contract 75N92023D00011, and by a grant from The Roy J. Carver Charitable Trust (19-5154). The COPDGene study (NCT00608764) has also been supported by the COPD Foundation through contributions made to an Industry Advisory Committee that has included AstraZeneca, Bayer Pharmaceuticals, Boehringer-Ingelheim, Genentech, GlaxoSmithKline, Novartis, Pfizer, and Sunovion.