bluuebunny/crossref_metadata_2025 huggingface dataset:
Suppression of anthracnose disease by orsellinaldehyde isolated from the mushroom Coprinus comatus
Authors: Cabutaje Enrico M , Ueno Kotomi , dela Cruz Thomas Edison E , Ishihara Atsushi
Published: May 2024

Aims

Anthracnose caused by Colletotrichum species is one of the most devastating diseases of fruits and crops. We isolated and identified an antifungal compound from the mushroom Coprinus comatus and investigated its inhibitory potential against anthracnose disease-causing fungi with the goal of discovering natural products that can suppress anthracnose-caused plant disease.

Methods and results

The culture filtrate of C. comatus was subjected to a bioassay-guided isolation of antifungal compounds. The active compound was identified as orsellinaldehyde (2,4-dihydroxy-6-methylbenzaldehyde) based on mass spectroscopy and nuclear magnetic resonance analyses. Orsellinaldehyde displayed broad-spectrum inhibitory activity against different plant pathogenic fungi. Among the tested Colletotrichum species, it exhibited the lowest IC50 values on conidial germination and germ tube elongation of Colletotrichum orbiculare. The compound also showed remarkable inhibitory activity against Colletotrichum gloeosporiodes. The staining of Colletotrichum conidia with fluorescein diacetate and propidium iodide demonstrated that the compound is fungicidal. The postharvest in-vivo detached fruit assay indicated that orsellinaldehyde suppressed anthracnose lesion symptoms on mango and cucumber fruits caused by C. gloeosporioides and C. orbiculare, respectively.

Conclusions

Orsellinaldehyde was identified as a potent antifungal compound from the culture filtrate of C. comatus. The inhibitory and fungicidal activities of orsellinaldehyde against different Colletotrichum species indicate its potential as a fungicide for protecting various fruits against anthracnose disease-causing fungi.
Imiglucerase, cholecalciferol, and bone-diet in skeletal health management of type I Gaucher disease patients: a pilot study and systematic review
Authors: Barbato Antonio , Vergatti Anita , Giaquinto Alfonso , Pizzulo Ilaria Libera , Perna Ludovica , Perruolo Giuseppe , Abate Veronica , Sibilio Michelina , Mainolfi Ciro , Soscia Ernesto , De Filippo Gianpaolo , Formisano Pietro , Galletti Ferruccio , Strazzullo Pasquale , Rendina Domenico
Published: May 2024

Skeletal anomalies represent a characteristic feature of type 1 Gaucher disease (GD1). Here we evaluated the impact of an integrated therapy comprising enzyme-replacement therapy (ERT), cholecalciferol, and a normocalcemic-normocaloric-hyposodic diet (bone diet) on bone health in GD1 patients. We also performed a systematic review to compare our results with available data. From January 1, 2015 to February 28, 2019, all GD1 patients referred to Federico II University were enrolled and treated with the integrated therapy. Bone turnover markers and bone mineral density (BMD) were evaluated at baseline (T0) and after 24 months (T24). We enrolled 25 GD1 patients, all showing 25-hydroxy vitamin D (25OHD) levels < 50 nmol/l (hypovitaminosis D) at T0. Response to cholecalciferol treatment was effective, showing a direct relationship between 25OHD levels before and after treatment. At T0, 2 GD1 patients showed fragility fractures, 5 the Erlenmeyer flask deformity, 3 osteonecrosis, and 7 a BMD Z-score ≤ –2. Overall, GD1 patients with bone anomalies showed higher C-terminal telopeptide levels compared with those without bone anomalies. No new bone anomalies occurred during 2 years of follow-up. At T24, BMD remained stable across the entire study cohort, including in patients with bone anomalies. The systematic review showed that our study is the first that evaluated all bone health parameters. Hypovitaminosis D is prevalent in GD1 patients. The response to cholecalciferol treatment was effective but different to healthy subjects and in patients with metabolic bone disorders. Integrated therapy including ERT, cholecalciferol, and bone diet guarantees bone health.
Machine overstrain prediction for early detection and effective maintenance: A machine learning algorithm comparison
Authors: Mota Bruno , Faria Pedro , Ramos Carlos
Published: May 2024

Machine stability and energy efficiency have become major issues in the manufacturing industry, primarily during the COVID-19 pandemic where fluctuations in supply and demand were common. As a result, Predictive Maintenance (PdM) has become more desirable, since predicting failures ahead of time allows to avoid downtime and improves stability and energy efficiency in machines. One type of machine failure stands out due to its impact, machine overstrain, which can occur when machines are used beyond their tolerable limit. From the current literature, there are little to no relevant works that focus on machine overstrain failure detection or prediction. Accordingly, the purpose of this paper is to implement and compare four Machine Learning (ML) algorithms for PdM applied to machine overstrain failures: Artificial Neural Network (ANN), Gradient Boosting, Random Forest and Support Vector Machine (SVM). Moreover, it proposes a training methodology for imbalanced data and the automatic optimization of hyperparameters, which aims to improve performance in the ML models. To evaluate the performance of the ML models, a synthetic dataset that simulates industrial machine data is used. The obtained results show the robustness of the proposed methodology, with the ANN and SVM models achieving a perfect recall score, with 98.95% and 98.85% in accuracy, respectively.
Enhancing buoy-based swinging energy harvesters through bat algorithm optimization: a comprehensive study
Authors: Chiu Min-Chie , Cheng Ho-Chih
Published: May 2024

Due to the threat of greenhouse gas emissions on Earth's sustainability, low carbon with green energy is crucial. Ocean hydropower is inexhaustible, with wave energy being a feasible green energy source. Previous low-frequency domain wave energy capture mainly used linear piston-type electromagnetic induction generators. However, this method produced weak electrical energy. To address this, a novel wave power generation method is proposed. It involves setting up a raft-like float, which is pushed by waves. A spring and damping assembly for buffering is added between the float and a vertical rod. The spring and damping assembly connect to a rod element online, and through a rod and gear mechanism, convert the float's linear motion into oscillatory motion to drive a generator. A raft-style float for sufficient buoyancy and a rod and gear mechanism to convert linear motion into rotational motion, driving a generator is adopted to produce more significant electrical energy. This study adopts a Lagrangian energy method and complex variable functions to deal with a double-mass dynamic system. Additionally, using a surface sinusoidal wave with amplitude of 0.3 m and a frequency of 2 rad/s as an example, the study combines bat algorithms to optimize the energy harvester for maximum power generation. Consequently, simulations demonstrate a maximal electrical power output of 4470 watts. The applied force and moment on the gear to induce electrical power measure 19 000 N and 5700 N-m, respectively.
Cecal volvolus herniation through the Winslow Foramen: a case report and literature review of surgical management
Authors: Gramellini Marco , Solimene Folco , Menz Moritz , Hinterleitner Lorenz , Breitenstein Stefan , Kambakamba Patryk
Published: May 2024

Both cecal volvolus and Winslow hernia are rare clinical presentations accounting for 1–1.5 and 0.08% of bowel obstructions. The combination of the two phenomena has been described so far in 13 case reports. Our patient underwent laparotomy with lesser Sac opening, manual hernia reduction, right hemicolectomy and partial Foramen closure with two simple stitches of PDS 4.0. Due to the scarcity of literature guidelines are not available, the intraoperative state of the tissues and the likelihood of a hernia recurrence play a decisive role in surgical management.
Delayed onset of Corynebacterium simulans infection following open reduction and internal fixation of a trimalleolar fracture
Authors: Tsivelekas Konstantinos , Lykos Stavros , Pallis Dimitrios , Ampadiotaki Margarita-Michaela , Nikolakakos Petros , Tilentzoglou Anastasia , Papadakis Stamatios A
Published: May 2024

Surgical site infections (SSIs) following open reduction and internal fixation (ORIF) of ankle fractures can lead to significant disability. This case report emphasizes a unique instance of SSI caused by Corynebacterium simulans, following ORIF of a trimalleolar ankle fracture in a 55-year-old female patient. To our knowledge, this is the first reported case of C. simulans infection after ORIF in the literature. The pathogen was detected after surgical debridement, removal and sonication of the hardware, and identified through matrix assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) and 16S rRNA gene sequencing. Specific intravenous antibiotic regimen was administered for a total duration of 4 weeks. During the 12th month follow-up, the patient presented no signs of infection and an excellent clinical outcome. This case report underscores the need for alertness regarding atypical pathogens in postoperative complications and the critical role of precise microbial diagnosis in managing rare orthopaedic infections.
Treatment outcomes of cochlear implantation in pediatric patients with Cockayne syndrome type I: a case series
Authors: Kostova Mariana , Banerjee Anirvan
Published: May 2024

This retrospective case series evaluates treatment outcomes post-cochlear implantation in pediatric patients diagnosed with Cockayne syndrome (CS) and bilateral sensorineural hearing loss. Two female pediatric patients with CS type I underwent either bilateral or unilateral cochlear implantation. Visual reinforcement audiometry (VRA) and postoperative cochlear implant tolerance were the main outcome measures. Patient 1 demonstrated notable improvements in VRA results and school performance following bilateral implantation. Patient 2 experienced enhanced quality of life and environmental awareness post-unilateral implantation, despite a lack of objective VRA results due to developmental delay. The study underscores the benefits of cochlear implantation in CS patients, especially in patients who are post-lingual or with better cognitive function.
Modeling the potential impact of a sugar-sweetened beverage tax on ischemic heart disease and stroke in Brazil
Authors: Rinaldi Ana Elisa M , Nucci Luciana Bertoldi , Enes Carla Cristina
Published: May 2024

Background

A high intake of sugar-sweetened beverages (SSBs) is associated with the risk of several chronic diseases, including ischemic heart disease (IHD) and stroke. This study aimed to model the impact of a 20% tax on all SSBs for IHD and stroke among Brazilian adults.

Methods

This was an ex-ante risk comparative study. The model applied a 20% tax on SSBs and projected the incidence, prevalence and mortality of IHD and stroke over a 20-year period (2019–39). Using data on consumption, previously published cross- and own-price elasticities of SSBs, and relative risk, we estimated changes in IHD and stroke burden.

Results

Our model predicts that a 20% SSB tax may reduce new cases of IHD by ~13%, especially among women, and avert ~8% of the deaths attributable to IHD over 20 years. These results represent a decrease of 19 543 new cases and 8466 and 7274 fewer deaths in the period for men and women, respectively. Estimates of reduction in incidence, prevalence and deaths from stroke were not significant over 20 years.

Conclusions

Even under conservative assumptions, our study found that a small reduction in SSB consumption led to a substantial decrease in IHD incidence and mortality in Brazil.
Transport activity regulates mitochondrial bioenergetics and biogenesis in renal tubules
Authors: Cheng Chih‐Jen , Nizar Jonathan M. , Dai Dao‐Fu , Huang Chou‐Long
Published: May 2024

Renal tubules are featured with copious mitochondria and robust transport activity. Mutations in mitochondrial genes cause congenital renal tubulopathies, and changes in transport activity affect mitochondrial morphology, suggesting mitochondrial function and transport activity are tightly coupled. Current methods of using bulk kidney tissues or cultured cells to study mitochondrial bioenergetics are limited. Here, we optimized an extracellular flux analysis (EFA) to study mitochondrial respiration and energy metabolism using microdissected mouse renal tubule segments. EFA detects mitochondrial respiration and glycolysis by measuring oxygen consumption and extracellular acidification rates, respectively. We show that both measurements positively correlate with sample sizes of a few centimeter‐length renal tubules. The thick ascending limbs (TALs) and distal convoluted tubules (DCTs) critically utilize glucose/pyruvate as energy substrates, whereas proximal tubules (PTs) are significantly much less so. Acute inhibition of TALs’ transport activity by ouabain treatment reduces basal and ATP‐linked mitochondrial respiration. Chronic inhibition of transport activity by 2‐week furosemide treatment or deletion of with‐no‐lysine kinase 4 (Wnk4) decreases maximal mitochondrial capacity. In addition, chronic inhibition downregulates mitochondrial DNA mass and mitochondrial length/density in TALs and DCTs. Conversely, gain‐of‐function Wnk4 mutation increases maximal mitochondrial capacity and mitochondrial length/density without increasing mitochondrial DNA mass. In conclusion, EFA is a sensitive and reliable method to investigate mitochondrial functions in isolated renal tubules. Transport activity tightly regulates mitochondrial bioenergetics and biogenesis to meet the energy demand in renal tubules. The system allows future investigation into whether and how mitochondria contribute to tubular remodeling adapted to changes in transport activity.
Regorafenib in patients with pretreated advanced melanoma: a single-center case series
Authors: Vander Mijnsbrugge An-Sofie , Cerckel J , Dirven I , Tijtgat J , Vounckx M , Claes N , Neyns Bart
Published: May 2024

Melanoma patients failing all approved treatment options have a poor prognosis. The antimelanoma activity of regorafenib (REGO), a multitargeted kinase inhibitor, has not been investigated in this patient population. The objective response rate and safety of REGO treatment in advanced melanoma patients was investigated retrospectively. Twenty-seven patients received REGO treatment. All patients had progressed on anti–programmed cell death protein 1 (PD-1) and anti–cytotoxic T-lymphocyte–associated protein 4 (CTLA-4) checkpoint inhibition and BRAF/MEK inhibitors (in case of a BRAF 
V600mutation). REGO was administered in continuous dosing and combined (upfront or sequentially) with nivolumab (n = 5), trametinib (n = 8), binimetinib (n = 2), encorafenib (n = 1), dabrafenib/trametinib (n = 9), or encorafenib/binimetinib (n = 7). The best overall response was partial response (PR) in five patients (18.5%) and stable disease in three patients (11.1%). Three of seven (42.8%) BRAF 
 V600mut patients treated with REGO in combination with BRAF/MEK inhibitors obtained a PR (including regression of brain metastases in all three patients). In addition, PR was documented in a BRAF 
V600mut patient treated with REGO plus anti-PD-1, and a NRAS
Q61mut patient treated with REGO plus a MEK inhibitor. Common grade 3–4 treatment-related adverse events included arterial hypertension (n = 7), elevated transaminase levels (n = 5), abdominal pain (n = 3), colitis (n = 2), anorexia (n = 1), diarrhea (n = 1), fever (n = 1), duodenal perforation (n = 1), and colonic bleeding (n = 1). Median progression-free survival was 11.0 weeks (95% confidence interval, 7.1–14.9); median overall survival was 23.1 weeks (95% confidence interval, 13.0–33.3). REGO has a manageable safety profile in advanced melanoma patients, in monotherapy as well as combined with BRAF/MEK inhibitors or PD-1 blocking monoclonal antibodies. The triplet combination of REGO with BRAF/MEK inhibitors appears most active, particularly in the BRAF
 V600mut patients.
Scalp Composite Tissue Transplantation for Repairing Upper Lip Defect: A Feasible Clinical Study
Authors: Liu Jia , Wei Jiao , Dai Chuan-Chang , Yu Bao-Fu
Published: May 2024

Background:

The repair of upper lip defects is difficult and can result in asymmetry. The authors have developed a postauricular scalp composite tissue for the repair of upper lip defects. Herein, the authors, present the feasibility of scalp composite tissue grafts for repairing of upper lip defects.

Methods:

The authors conducted a retrospective study of 10 patients who underwent scalp composite tissue transplantation for upper lip repair. The surgical procedure consisted of the excision of skin lesions or scar tissue from the upper lip to prepare the recipient area, and then the scalp composite tissue was excised behind the ear and transplanted to the upper lip defect. The authors reviewed the photographs and clinical notes of these patients. The patients’ self-reported satisfaction with the repair effect was assessed. Tissue sections and hematoxylin and eosin staining of the scalp composite tissues were performed.

Results:

All patients successfully underwent lesion resection and scalp composite tissue transplantation to repair the wound. There was no necrosis of the scalp composite tissue in the early postoperative period. The lip wound healed completely within 2 weeks. The mean follow-up time was 16 months, ranging from 12 to 20 months. Histologic sections and hematoxylin and eosin staining showed that the scalp composite tissue had abundant capillaries and dense fibrous connective tissue. All 10 patients were satisfied with the clinical effect of the procedure.

Conclusion:

Scalp composite tissue transplantation is a viable method for repairing upper lip defects. The special histomorphological characteristics of the scalp provide the basis for clinical application.

Level of evidence:

IV.
Absence of c-Maf and IL-10 enables Type I IFN enhancement of innate responses to low-dose LPS in alveolar macrophages
Authors: Lim Pamelia N. , Cervantes Maritza M. , Pham Linh K. , Doherty Sydney , Tufts Ankita , Dubey Divya , Mai Dat , Aderem Alan , Diercks Alan H. , Rothchild Alissa C.
Published: May 2024

Alveolar macrophages (AMs) are lower-airway resident myeloid cells and are among the first to respond to inhaled pathogens. Here, we interrogate AM innate sensing to Pathogen Associated Molecular Patterns (PAMPs) and determine AMs have decreased responses to low- dose LPS compared to other macrophages, as measured by TNF, IL-6,Ifnb, andIfit3. We find the reduced response to low-dose LPS correlates with minimal TLR4 and CD14 surface expression, despite sufficient internal expression of TLR4. Additionally, we find that AMs do not produce IL-10 in response to a variety of PAMPs due to low expression of transcription factor c- Maf and that lack of IL-10 production contributes to an enhancement of pro-inflammatory responses by Type I IFN. Our findings demonstrate that AMs have cell-intrinsic dampened responses to LPS, which is enhanced by type I IFN exposure. These data implicate conditions where AMs may have reduced or enhanced sentinel responses to bacterial infections.

HIGHLIGHTS

Alveolar macrophages (AMs) do not produce TNF or IL-6 in response to low-dose LPS due to minimal surface expression of TLR4 and CD14

Lack of AM IL-10 production is dependent on low c-Maf expression

Exogenous c-Maf expression increases AM IL-10 production

IFNβ enhances AM TNF and IL-6 responses to low-dose LPS and this is dependent on a lack of IL-10
Machine learning assisted mid-infrared spectrochemical fibrillar collagen imaging in clinical tissues
Authors: Adi Wihan , Perez Bryan E. Rubio , Liu Yuming , Runkle Sydney , Eliceiri Kevin W. , Yesilkoy Filiz
Published: May 2024

Significance

Label-free multimodal imaging methods that can provide complementary structural and chemical information from the same sample are critical for comprehensive tissue analyses. These methods are specifically needed to study the complex tumor-microenvironment where fibrillar collagen’s architectural changes are associated with cancer progression. To address this need, we present a multimodal computational imaging method where mid-infrared spectral imaging (MIRSI) is employed with second harmonic generation (SHG) microscopy to identify fibrillar collagen in biological tissues.

Aim

To demonstrate a multimodal approach where a morphology-specific contrast mechanism guides a mid-infrared spectral imaging method to detect fibrillar collagen based on its chemical signatures.

Approach

We trained a supervised machine learning (ML) model using SHG images as ground truth collagen labels to classify fibrillar collagen in biological tissues based on their mid-infrared hyperspectral images. Five human pancreatic tissue samples (sizes are in the order of millimeters) were imaged by both MIRSI and SHG microscopes. In total, 2.8 million MIRSI spectra were used to train a random forest (RF) model. The remaining 68 million spectra were used to validate the collagen images generated by the RF-MIRSI model in terms of collagen segmentation, orientation, and alignment.

Results

Compared to the SHG ground truth, the generated MIRSI collagen images achieved a high average boundary F-score (0.8 at 4 pixels threshold) in the collagen distribution, high correlation (Pearson’s R 0.82) in the collagen orientation, and similarly high correlation (Pearson’s R 0.66) in the collagen alignment.

Conclusions

We showed the potential of ML-aided label-free mid-infrared hyperspectral imaging for collagen fiber and tumor microenvironment analysis in tumor pathology samples.
Number of Trials and E-Field Orientation during Continuous Theta Burst Stimulation May Impact Modulation of Motor-Evoked Potentials
Authors: Preis Silas , Kim Su Hwan , Schandelmaier Paul , Zimmer Claus , Meyer Bernhard , Krieg Sandro M. , Sollmann Nico , Schramm Severin
Published: May 2024

Introduction

Noninvasive neuromodulation (NM) via transcranial magnetic stimulation (TMS) is increasingly applied to treat neurological and psychiatric disorders. However, NM effects are highly variable between subjects. E-field orientation (EFO) during NM protocols may heavily contribute to this variability. Investigating the influence of EFO during NM could lead to improved therapeutic protocols by enabling more tailored approaches for patient-specific NM. In the present study, we aimed to examine the influence of varying EFO during continuous theta burst stimulation (cTBS) on the modulation of motor-evoked potentials (MEPs).

Methods

20 healthy volunteers (8 F; mean age 25.7±2.7 years) took part in this prospective, single blind sham-controlled crossover study consisting of three neuronavigated TMS sessions. The sessions differed only in EFO during cTBS (parallel to optimal EFO for MEP generation [OPT], 90° rotated from OPT [90], 45° rotated from OPT with 7.3 cm spacer [SHAM]). Electromyography was recorded from abductor pollicis brevis, first dorsal interosseous, and adductor digiti minimi muscles during stimulation of the abductor pollicis brevis (APB) motor hotspot. 4 blocks (PRE, POST1, POST2, POST3) with 30 MEPs each were elicited from the motor hotspot. Between the PRE and POST1 block, 40 s of cTBS were performed using one of the three EFO paradigms. Individual POST blocks were separated by a 2 min interval. MEPs were analyzed with linear mixed effects modeling augmented by bootstrapping.

Results

A total of 19,830 MEPs were analyzed. Progression through the trial blocks led to heightened MEP amplitudes (e.g., POST3 vs. PRE; log-estimate 0.244, t = 21.43), and later trials were significantly associated with higher MEP amplitudes (spearman’s rho 0.981; p < 0.001). Additionally, on the group level, a significant albeit slight influence of EFO on MEP amplitudes with the 90 paradigm leading to facilitation, and SHAM paradigm leading to suppression of MEP amplitudes was observed when compared to the OPT paradigm (log-estimate 90: 0.135, t = 13.604; log-estimate SHAM: −0.043, t = −4.283). On the subject level, we observed strong heterogeneity between individuals regarding their response to cTBS using varying EFO.

Discussion

We observed that MEP amplitudes following cTBS differed significantly based on EFO during NM. This implies that for a given desired NM result, individual EFO optimization may act as an avenue to maximize the NM effect. Therapeutic NM applications might consider EFO as a parameter of interest to be investigated in clinical studies. Additionally, prolonged single-pulse stimulation appeared to possess a NM quality of its own, which should be considered in TMS studies employing single-pulse protocols.
“Even things they won’t share with their sisters-in-law”– Assessing an integrated Community Health Worker intervention on person-centered postpartum contraception in rural Nepal
Authors: Choudhury Nandini , Wu Wan-Ju , Khatri Rekha , Tiwari Aparna , Thapa Aradhana , Adhikari Samrachna , Basnett Indira , Bhandari Ved , Bhatta Aasha , Bogati Bhawana , Bhatt Laxman Datt , Citrin David , Halliday Scott , Khadka Sonu , Ksetri Yashoda Kumari Bhat , Kunwar Lal Bahadur , Magar Kshitiz Rana , Marasini Nutan , Maru Duncan , Nirola Isha , Paudel Rashmi , Rai Bala , Schwarz Ryan , Saud Sita , Sharma Dikshya , Shrestha Goma Niroula , Shrestha Ramesh , Thapa Poshan , Rayamazi Hari Jung , Maru Sheela , Sapkota Sabitri
Published: May 2024

Postpartum contraceptive counseling and access are challenging in Nepal’s remote, hilly areas, driving a disproportionately higher unmet need for contraception. Community health workers (CHWs) play an important role in delivering healthcare in difficult to reach places in Nepal, but there is limited evidence on the ideal CHW model and its impact over time. We implemented a pilot program in two rural districts in Nepal where full-time, salaried, and supervised CHWs delivered a bundled reproductive, maternal, newborn, and child health (RMNCH) intervention. This included a person-centered contraceptive counseling component adapted from the Balanced Counseling Strategy. Applying a type 2 hybrid effectiveness-implementation study approach, we conducted a non-randomized pre-post study with repeated measurements and nested qualitative data collection to assess the intervention’s reach, effectiveness, adoption, implementation, and maintenance. This paper describes the postpartum contraceptive outcomes associated with the integrated RMNCH intervention over a five-year period. Compared to the pre-intervention period, we observed a higher ward-level post-intervention postpartum contraceptive prevalence stratified by early postpartum (RR: 2.20; 95% CI: 1.96, 2.48) and late postpartum (RR: 1.70; 95% CI: 1.50, 1.93) periods, after adjusting for district and intervention site. Although we observed high rates of lactational amenorrhea method (LAM) in most intervention sites, the proportion of women who switched from LAM to another effective method was relatively low. Qualitative data indicate that CHWs’ longitudinal engagement enabled them to build trust with participants in their community, which likely contributed to their uptake of modern contraceptive methods. Barriers to modern contraceptive use included fear of side effects, limited autonomy for women, peer influence, and contraceptive unavailability. Implementation barriers included distance, challenging physical terrain, and increased travel times during the rainy season. This study contributes to the implementation research literature on community-based interventions to improve postpartum contraception use and may inform other CHW programs in similar contexts.
The importance of small island populations for the long-term survival of endangered large-bodied insular mammals
Authors: Aninta Sabhrina Gita , Drinkwater Rosie , Carmagnini Alberto , Deere Nicolas J. , Priyono Dwi Sendi , Andayani Noviar , Winarni Nurul L. , Supriatna Jatna , Fumagalli Matteo , Larson Greger , Galbusera Peter H.A. , Macdonald Alastair , Greer Deborah , Mohamad Kusdiantoro , Prasetyaningtyas Wahono Esthi , Mustari Abdul Haris , Williams John Lewis , Barnett Ross , Semiadi Gono , Burton James , Seaman David , Voigt Maria , Struebig Matthew , Brace Selina , Rossiter Stephen , Frantz Laurent
Published: May 2024

Island populations of large vertebrates have experienced higher extinction rates than mainland populations over long timescales due to demographic stochasticity, genetic drift and inbreeding. Conversely, small island populations often experience relatively less anthropogenic habitat degradation than populations on larger islands, making them potential targets for conservation interventions such as genetic rescue to improve their overall genetic diversity. Here we determine the consequences and conservation implications of long-term isolation and recent human activities on genetic diversity of island populations of two forest-dependent mammals endemic to the Wallacea archipelago: the anoa (Bubalusspp.) and babirusa (Babyrousaspp.). Using genomic analyses and habitat suitability models, we show that, compared to closely related species, populations on mainland Sulawesi exhibit low heterozygosity, high inbreeding, and a high proportion of deleterious alleles. In contrast, populations on smaller islands possess fewer deleterious mutations despite exhibiting lower heterozygosity and higher inbreeding. Site frequency spectra indicate that these patterns reflect stronger, long-term purging in smaller island populations. Our results thus suggest that conservation efforts should focus on protecting small island habitats and avoiding translocations from mainland populations. This study highlights the crucial role of small offshore islands for the long-term survival of Wallacea’s iconic and indigenous mammals in the face of development on the mainland.

Significance statement

Within tropical archipelagos, such as the Wallacea biodiversity hotspot, larger islands experience greater resource exploitation compared to smaller ones, highlighting the potential of smaller islands as refuges for conservation. To investigate the genetic health of populations on small islands, we used genomic, occurrence, and environmental data from a system of replicated populations of anoa and babirusa across islands of varying sizes. In contrast to larger islands like Sulawesi, our results demonstrate that smaller offshore islands not only provide higher-quality habitats but also support populations that have efficiently purged harmful mutations. Thus, despite their known vulnerability over geological time-frames, small island populations can provide long term insurance against human-driven extinction and conservation efforts should prioritise habitat management over translocations.
Identification of 17 novel epigenetic biomarkers associated with anxiety disorders using differential methylation analysis followed by machine learning-based validation
Authors: Kwon Yoonsung , Blazyte Asta , Jeon Yeonsu , Kim Yeo Jin , An Kyungwhan , Jeon Sungwon , Ryu Hyojung , Shin Dong-Hyun , Ahn Jihye , Um Hyojin , Kang Younghui , Bak Hyebin , Kim Byoung-Chul , Lee Semin , Jung Hyung-Tae , Shin Eun-Seok , Bhak Jong
Published: May 2024

Background

The changes in DNA methylation patterns may reflect both physical and mental well-being, the latter being a relatively unexplored avenue in terms of clinical utility for psychiatric disorders. In this study, our objective was to identify the methylation-based biomarkers for anxiety disorders and subsequently validate their reliability.

Methods

A comparative differential methylation analysis was performed on whole blood samples from 94 anxiety disorder patients and 296 control samples using targeted bisulfite sequencing. Subsequent validation of identified biomarkers employed an artificial intelligence- based risk prediction models: a linear calculation-based methylation risk score model and two tree-based machine learning models: Random Forest and XGBoost.

Results

17 novel epigenetic methylation biomarkers were identified to be associated with anxiety disorders. These biomarkers were predominantly localized near CpG islands, and they were associated with two distinct biological processes: 1) cell apoptosis and mitochondrial dysfunction and 2) the regulation of neurosignaling. We further developed a robust diagnostic risk prediction system to classify anxiety disorders from healthy controls using the 17 biomarkers. Machine learning validation confirmed the robustness of our biomarker set, with XGBoost as the best-performing algorithm, an area under the curve of 0.876.

Conclusion

Our findings support the potential of blood liquid biopsy in enhancing the clinical utility of anxiety disorder diagnostics. This unique set of epigenetic biomarkers holds the potential for early diagnosis, prediction of treatment efficacy, continuous monitoring, health screening, and the delivery of personalized therapeutic interventions for individuals affected by anxiety disorders.
A tale of two n-backs: Diverging associations of dorsolateral prefrontal cortex activation with n-back task performance
Authors: Tubiolo Philip N. , Williams John C. , Van Snellenberg Jared X.
Published: May 2024

Background

In studying the neural correlates of working memory (WM) ability via functional magnetic resonance imaging (fMRI) in health and disease, it is relatively uncommon for investigators to report associations between brain activation and measures of task performance. Additionally, how the choice of WM task impacts observed activation-performance relationships is poorly understood. We sought to illustrate the impact of WM task on brain-behavior correlations using two large, publicly available datasets.

Methods

We conducted between-participants analyses of task-based fMRI data from two publicly available datasets: the Human Connectome Project (HCP; n = 866) and the Queensland Twin Imaging (QTIM) Study (n = 459). Participants performed two distinct variations of then-back WM task with different stimuli, timings, and response paradigms. Associations between brain activation ([2-back − 0-back] contrast) and task performance (2-back % correct) were investigated separately in each dataset, as well as across datasets, within the dorsolateral prefrontal cortex (dlPFC), medial prefrontal cortex, and whole cortex.

Results

Global patterns of activation to task were similar in both datasets. However, opposite associations between activation and task performance were observed in bilateral pre-supplementary motor area and left middle frontal gyrus. Within the dlPFC, HCP participants exhibited a significantly greater activation-performance relationship in bilateral middle frontal gyrus relative to QTIM Study participants.

Conclusions

The observation of diverging activation-performance relationships between two large datasets performing variations of then-back task serves as a critical reminder for investigators to exercise caution when selecting WM tasks and interpreting neural activation in response to a WM task.
Predicting and Shaping Human-Machine Interactions in Closed-loop, Co-adaptive Neural Interfaces
Authors: Madduri Maneeshika M. , Yamagami Momona , Li Si Jia , Burckhardt Sasha , Burden Samuel A. , Orsborn Amy L.
Published: May 2024

Neural interfaces can restore or augment human sensorimotor capabilities by converting high-bandwidth biological signals into control signals for an external device via a decoder algorithm. Leveraging user and decoder adaptation to create co-adaptive interfaces presents opportunities to improve usability and personalize devices. However, we lack principled methods to model and optimize the complex two-learner dynamics that arise in co-adaptive interfaces. Here, we present new computational methods based on control theory and game theory to analyze and generate predictions for user-decoder co-adaptive outcomes in continuous interactions. We tested these computational methods using an experimental platform where human participants (N=14) learn to control a cursor using an adaptive myoelectric interface to track a target on a computer display. Our framework predicted the outcome of co-adaptive interface interactions and revealed how interface properties can shape user behavior. These findings contribute new tools to design personalized, closed-loop, co-adaptive neural interfaces.
Early-Life Gut Inflammation Drives Sex-Dependent Shifts in the Microbiome-Endocrine-Brain Axis
Authors: Sullivan Olivia , Sie Claire , Ng Katharine M , Cotton Sophie , Rosete Cal , Hamden Jordan E , Singh Ajay Paul , Lee Kristen , Choudhary Jatin , Kim Jennifer , Yu Huaxu , Clayton Charlotte , Garcia Natalia A Carranza , Voznyuk Kateryna , Deng Brian D , Plett Nadine , Arora Sana , Ghezzi Hans , Huan Tao , Soma Kiran K , Yu John-Paul J , Tropini Carolina , Ciernia Annie Vogel
Published: May 2024

Despite recent advances in understanding the connection between the gut microbiota and the adult brain, there remains a wide knowledge gap in how gut inflammation impacts brain development. We hypothesized that intestinal inflammation in early life would negatively affect neurodevelopment through dysregulation of microbiota communication to the brain. We therefore developed a novel pediatric chemical model of inflammatory bowel disease (IBD), an incurable condition affecting millions of people worldwide. IBD is characterized by chronic intestinal inflammation, and has comorbid symptoms of anxiety, depression and cognitive impairment. Significantly, 25% of patients with IBD are diagnosed during childhood, and the effect of chronic inflammation during this critical period of development is largely unknown. This study investigated the effects of early-life gut inflammation induced by DSS (dextran sulfate sodium) on a range of microbiota, endocrine, and behavioral outcomes, focusing on sex-specific impacts. DSS-treated mice exhibited increased intestinal inflammation, altered microbiota membership, and changes in microbiota-mediated circulating metabolites. The majority of behavioral measures were unaffected, with the exception of impaired mate-seeking behaviors in DSS-treated males. DSS-treated males also showed significantly smaller seminal vesicles, lower circulating androgens, and decreased intestinal hormone-activating enzyme activity. In the brain, microglia morphology was chronically altered with DSS treatment in a sex-specific manner. The results suggest that early-life gut inflammation causes changes in gut microbiota composition, affecting short-chain fatty acid (SCFA) producers and glucuronidase (GUS) activity, correlating with altered SCFA and androgen levels. The findings emphasize the developmental sensitivity to inflammation-induced changes in endocrine signalling and underscore long-lasting physiological and microbiome changes associated with juvenile IBD.
Dengue NS1 interaction with lipids alters its pathogenic effects on monocyte derived macrophages
Authors: Dayarathna Shashika , Senadheera Bhagya , Jeewandara Chandima , Dissanayaka Madushika , Bary Farha , Ogg Graham S. , Malavige Gathsaurie Neelika
Published: May 2024

Background

While dengue NS1 antigen has been shown to be associated with disease pathogenesis in some studies, it has not been linked in other studies, with the reasons remaining unclear. NS1 antigen levels in acute dengue are often associated with increased disease severity, but there have been a wide variation in results based on past dengue infection and infecting dengue virus (DENV) serotype. As NS1 engages with many host lipids, we hypothesize that the type of NS1-lipid interactions alters its pathogenicity.

Methods

Primary human monocyte derived macrophages (MDMs) were co-cultured with NS1 alone or with HDL, LDL, LPS and/or platelet activating factor (PAF) from individuals with a history of past dengue fever (DF=8) or dengue haemorrhagic fever (DHF=8). IL-1β levels were measured in culture supernatants, and gene expression analysis carried out in MDMs. Monocyte subpopulations were assessed by flow cytometry. Hierarchical cluster analysis with Euclidean distance calculations were used to differentiate clusters. Differentially expressed variables were extracted and a classifier model was developed to differentiate between past DF and DHF.

Results

Significantly higher levels of IL-1β were seen in culture supernatants when NS1 was co-cultured with LDL (p=0.01), but with lower levels with HDL (p=0.05). MDMs of those past DHF produced more IL-1β when NS1 with PAF (p=0.02). MDMs of individuals with past DHF, were significantly more likely to down-regulateRPLP2gene expression when macrophages were co-cultured with either PAF alone, or NS1 combined with PAF, or NS1 combined with LDL. When NS1 was co-cultured with PAF, HDL or LDL two clusters were detected based onIL10expression, but these did not differentiate those with past DF or DHF.

Conclusions

As RPLP2 is important in DENV replication and in regulating cellular stress responses and immune responses and IL-10 is associated with severe disease, it would be important to further explore how differential expression of RPLP2 and IL-10 could lead to disease pathogenesis based on NS1 and lipid interactions.
Multimodal identification of the mouse brain using simultaneous Ca2+imaging and fMRI
Authors: Mandino Francesca , Horien Corey , Shen Xilin , Desrosiers-Grégoire Gabriel , Luo Wendy , Markicevic Marija , Todd Constable R. , Papademetris Xenophon , Chakravarty Mallar M. , Betzel Richard F. , Lake Evelyn M.R.
Published: May 2024

Individual differences in neuroimaging are of interest to clinical and cognitive neuroscientists based on their potential for guiding the personalized treatment of various heterogeneous neurological conditions and diseases. Despite many advantages, the workhorse in this arena, BOLD (blood-oxygen-level-dependent) functional magnetic resonance imaging (fMRI) suffers from low spatiotemporal resolution and specificity as well as a propensity for noise and spurious signal corruption. To better understand individual differences in BOLD-fMRI data, we can use animal models where fMRI, alongside complementary but more invasive contrasts, can be accessed. Here, we apply simultaneous wide-field fluorescence calcium imaging and BOLD-fMRI in mice to interrogate individual differences using a connectome-based identification framework adopted from the human fMRI literature. This approach yields high spatiotemporal resolution cell-type specific signals (here, from glia, excitatory, as well as inhibitory interneurons) from the whole cortex. We found mouse multimodal connectome-based identification to be successful and explored various features of these data.
Skeletal myotubes expressing ALS mutant SOD1 induce pathogenic changes, impair mitochondrial axonal transport, and trigger motoneuron death
Authors: Martínez Pablo , Silva Mónica , Abarzúa Sebastián , Tevy María Florencia , Jaimovich Enrique , Constantine-Paton Martha , Bustos Fernando J , van Zundert Brigitte
Published: May 2024

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of motoneurons (MNs), and despite progress, there is no effective treatment. A large body of evidence shows that astrocytes expressing ALS-linked mutant proteins cause non-cell autonomous toxicity of MNs. Although MNs innervate muscle fibers and ALS is characterized by the early disruption of the neuromuscular junction (NMJ) and axon degeneration, there are controversies about whether muscle contributes to non-cell-autonomous toxicity to MNs. In this study, we generated primary skeletal myotubes from myoblasts derived from ALS mice expressing human mutant SOD1G93A(termed hereafter mutSOD1). Characterization revealed that mutSOD1 skeletal myotubes display intrinsic phenotypic and functional differences compared to control myotubes generated from non-transgenic (NTg) littermates. Next, we analyzed whether ALS myotubes exert non-cell-autonomous toxicity to MNs. We report that conditioned media from mutSOD1 myotubes (mutSOD1-MCM), but not from control myotubes (NTg-MCM), induced robust death of primary MNs in mixed spinal cord cultures and compartmentalized microfluidic chambers. Our study further revealed that applying mutSOD1-MCM to the MN axonal side in microfluidic devices rapidly reduces mitochondrial axonal transport while increasing Ca2+ transients and reactive oxygen species (i.e., H2O2). These results indicate that soluble factor(s) released by mutSOD1 myotubes cause MN axonopathy that leads to lethal pathogenic changes.
Deep learning and eye-tracking for accurate EOG rejection
Authors: Huberty Scott , O’Reilly Christian
Published: May 2024

Electroencephalography (EEG) is a neuroimaging technique used to record the electrical activity generated by the brain. EEG recordings are often contaminated by various artifacts, notably those caused by eye movements and blinks (EOG artifacts). Independent component analysis (ICA) is commonly applied to isolate EOG artifacts and subtract the corresponding independent components from the EEG signals. However, ICA is an unsupervised technique that contains no knowledge of the eye movements during the task or the generative process by which these movements result in EOG artifacts. It is generally difficult to assess whether subtracting EOG components estimated through ICA removes some neurogenic activity. To address this limitation, we developed a deep learning model for EOG artifact removal that exploits information about eye movements available through eye-tracking. We leveraged theLarge Gridtask from the open-source EEGEyeNet dataset to develop and validate this approach. In this task, 30 participants looked at a series of dots appearing at 25 predetermined positions on the screen (810 trials/participant). EEG and eye-tracking were collected simultaneously. In this paper, we show that we can train a long short-term memory (LSTM) model to predict the component of EEG signals predictable from eye-tracking data. We further used this eye-tracking-informed evaluation of EOG artifacts to investigate the sensitivity and specificity of ICA, currently the dominant approach for EOG artifact correction. Our analysis indicates that although ICA is very sensitive to EOG, it has a comparatively low specificity.
Heartbeat perception is causally linked to frontal delta oscillations
Authors: Haslacher David , Reber Philipp , Cavallo Alessia , Rosenthal Annika , Pangratz Elisabeth , Beck Anne , Romanczuk-Seiferth Nina , Nikulin Vadim , Villringer Arno , Soekadar Surjo R.
Published: May 2024

The ability to accurately perceive one’s own bodily signals, such as the heartbeat, plays a vital role in physical and mental health. However, the neurophysiological mechanisms underlying this ability, termed interoception, are not fully understood. Converging evidence suggests that cardiac rhythms are linked to frontal brain activity, particularly oscillations in the delta (0.5 – 4 Hz) band, but their causal relationship remained elusive. Using amplitude-modulated transcranial alternating current stimulation (AM-tACS), a method to enhance or suppress brain oscillations in a phase-specific manner, we investigated whether frontal delta oscillations are causally linked to heartbeat perception. We found that enhancement of delta phase synchrony suppressed heartbeat detection accuracy, while suppression of delta phase synchrony enhanced heartbeat detection accuracy. These findings suggest that frontal delta oscillations play a critical role in heartbeat perception, paving the way for causal investigations of interoception and potential clinical applications.

Significance

Although bodily signals are known to influence perception and behavior, little is known about the underlying neurophysiological mechanisms. Here, we show that perception of the heartbeat is anticorrelated with phase synchrony of frontal delta oscillations, and that modulating these oscillations with transcranial electric stimulation influences heartbeat perception. Our results suggest that delta oscillations play a key role in processing bodily signals, with potential implications for theories of emotions and clinical neuroscience.