bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficient Federated Learning for Feature Aggregation with Heterogenous Edge Devices
Authors: Liu Fei , Xiong Zheng , Yu Wei , Wu Jia , Kong Zheng , Ji Yunhang , Xu Suwei , Ji Mingtao
Published: December 2023

Federated learning is a powerful distributed machine learning paradigm for feature aggregation and learning from multiple heterogenous edge devices, due to its ability to keep the privacy of data. However, the training is inefficient for heterogenous devices with considerable communication. Progressive learning is a promising approach for improving the efficiency. Since progressive learning partitions the training process into multiple stages, it is necessary to determine the number of rounds for each stage, and balance the trade-off between saving the energy and improving the model accuracy. Through pilot experiments, we find that the profile which reflects the relationship between round allocation and model quality remains similar in different hyper-parameter configurations, and also observe that the model quality is lossless if the complete model gets sufficient training. Based on the phenomena, we formulate an optimization problem which minimizes the energy consumption of all devices, under the constraint of model quality. We then design a polynomial-time algorithm for the problem. Experimental results demonstrate the superiority of our proposed algorithm under various settings.
A new method of crop yield prediction based on artificial intelligence
Authors: Zhang Yuanmin , Liao Yule , Li Yanjun
Published: December 2023

With the rapid growth of population, the continuous reduction of arable land and the acceleration of urbanization, the challenges facing agriculture are becoming increasingly severe. The rapid development of the new generation of digital economy, such as the industrial Internet, cloud computing and ChatGPT, has brought all-round impact on people’s lives and the global economy. At the same time, the changes of social economy and technology have promoted the development of agricultural production, and the application of intelligent stage number to create smart agriculture can improve the land output rate, labor productivity and resource utilization rate, and achieve sustainable agricultural development. Agricultural intelligence will become an important development direction of agriculture in the future. In this paper, an artificial intelligence-based method of crop yield prediction was proposed to improve the prediction accuracy of crop yield by using smart agriculture.
Prediction of deformation and damage of foundation support system based on BP neural network
Authors: Fan Haojie
Published: December 2023

The pit in the ground that needs to be excavated during the construction of a building is known as a foundation pit. In this paper, a MATLAB neural network toolbox is proposed to establish a three-layer BP neural network to predict building settlement. The relative error of the predicted values obtained after training is between -2% and 1%, and the maximum absolute error is 0.049 mm. this error is acceptable for rock-on-rock engineering problems. It shows that the building settlement prediction using artificial neural network method is feasible and the prediction results are credible. It automatically identifies the complex nonlinear relationships between the dependent and independent variables through self-learning of the optimal operation strategy, and considers the interactions among the factors in a comprehensive and integrated manner, which has good application prospects for solving nonlinear problems in the field of geotechnical engineering.
Recent H- ion source research and development at the Oak Ridge National Laboratory*
Authors: Welton R.F. , Han B.X. , Stockli M.P. , Murray S.N. , Pennisi T.R. , Stinson C. , Andzulis V. , Terszakowec G. , Piller C. , Tarvainen O. , Willis D.
Published: December 2023

The U.S. Spallation Neutron Source (SNS) is a state-of-the-art neutron scattering facility delivering the world's most intense pulsed neutron beams to a wide array of instruments which are used to conduct investigations in many fields of science and engineering. Neutrons are produced from spallation of liquid Hg by bombardment of short (∼1 μs), intense (∼35 A) pulses of protons delivered at 60 Hz by a storage ring which is fed by a high-intensity, ∼1 GeV H- LINAC. This facility has operated almost continuously since 2006, with ion source performance increasing over those years, and currently providing 50–60 mA of H- ions with a duty-factor of 6% for maintenance-free runs of several months with near 100% availability. Ion source research and development at ORNL has played a key role in enabling and supporting this success: this report provides an update on some of the ongoing ion source research and development efforts which have been undertaken since the previous Negative Ion Beams and Sources (NIBS) conference in 2020. These include significant improvements to H- beam current by extraction from a larger source outlet aperture and improvements to the electron dumping system which should eliminate the gradual loss of electrode voltage over the course of a run which has occasionally impacted SNS operations. Improvement and simplification of the plasma ignition system for the external antenna ion source, a long-standing problem, was also realized. Lastly, RF coupling efficiency was measured for both the SNS internal and external antenna ion sources.
A comprehensive analysis of cooling curves, fluidity, inclusions, porosity, and microstructure of NaCl-KCl-NaF flux treated Al-12Si alloy
Authors: Vijayan Vijeesh , Shetty Ashish , B N Pradeep , Hiremath Shivashankarayya , Kumar Pawan , H M Vishwanatha
Published: December 2023

In this study, we investigated the effects of treating Al-12 wt% silicon alloy with an equimolar composition mixture of NaCl, KCl, and NaF on various aspects of the alloy’s properties. Key findings of the research indicate that the flux treatment had significant effects on the alloy. It led to increased nucleation temperatures and reduced undercooling, thereby facilitating nucleation sites and grain refinement. Additionally, the inclusion of flux reduced the entrapment of inclusions in the melt, which can potentially enhance the mechanical properties of the alloy. However, it also led to a larger and more widely distributed gas porosity in the solidified samples, as gas evolved from the flux trapped during solidification. Moreover, the flux treatment had noticeable impacts on the morphology of eutectic silicon particles, reducing their aspect ratio. These findings offer valuable insights into the potential benefits and challenges of sodium-based flux melt treatment in optimizing the quality of Al-12Si alloy castings, particularly in die-casting applications.
Evaluation of manual and automated approaches for segmentation and extraction of quantitative indices from [18F]FDG PET-CT images
Authors: Krokos Georgios , Kotwal Tejas , Malaih Afnan , Barrington Sally , Jackson Price , Hicks Rodney J , Marsden Paul K , Fischer Barbara Malene
Published: December 2023

Utilisation of whole organ volumes to extract anatomical and functional information from computed tomography (CT) and positron emission tomography (PET) images may provide key information for the treatment and follow-up of cancer patients. However, manual organ segmentation, is laborious and time-consuming. In this study, a CT-based deep learning method and a multi-atlas method were evaluated for segmenting the liver and spleen on CT images to extract quantitative tracer information from Fluorine-18 fluorodeoxyglucose ([18F]FDG) PET images of 50 patients with advanced Hodgkin lymphoma (HL). Manual segmentation was used as the reference method. The two automatic methods were also compared with a manually defined volume of interest (VOI) within the organ, a technique commonly performed in clinical settings. Both automatic methods provided accurate CT segmentations, with the deep learning method outperforming the multi-atlas with a DICE coefficient of 0.93 ± 0.03 (mean ± standard deviation) in liver and 0.87 ± 0.17 in spleen compared to 0.87 ± 0.05 (liver) and 0.78 ± 0.11 (spleen) for the multi-atlas. Similarly, a mean relative error of −3.2% for the liver and −3.4% for the spleen across patients was found for the mean standardized uptake value (SUVmean) using the deep learning regions while the corresponding errors for the multi-atlas method were −4.7% and −9.2%, respectively. For the maximum SUV (SUVmax), both methods resulted in higher than 20% overestimation due to the extension of organ boundaries to include neighbouring, high-uptake regions. The conservative VOI method which did not extend into neighbouring tissues, provided a more accurate SUVmax estimate. In conclusion, the automatic, and particularly the deep learning method could be used to rapidly extract information of the SUVmean within the liver and spleen. However, activity from neighbouring organs and lesions can lead to high biases in SUVmax and current practices of manually defining a volume of interest in the organ should be considered instead.
The road(s) not taken—the past, present, and future of international investment law reform
Authors: Bjorklund Andrea K
Published: December 2023

In this 37th annual Freshfields Lecture, I explore several roads the international community could have taken in lieu of investor-state arbitration. What choices did they contemplate making – what roads did they consider taking – and what prompted them to make the choices they did? I titled the presentation the past, present, and future of reform of investment arbitration, and I will organize the talk around those three areas. First, I will talk about the past, and about four key choices the international community made over the course of the twentieth century that continue to affect the reform process. I’ll then address the present state of affairs at Working Group III, and how those decisions are influencing the reform process. I will close with a few projections about the future.
A neural circuit for spatial orientation derived from brain lesions
Authors: Roseman Moshe , Elias Uri , Kletenik Isaiah , Ferguson Michael A , Fox Michael D , Horowitz Zalman , Marshall Gad A , Spiers Hugo J , Arzy Shahar
Published: December 2023

There is disagreement regarding the major components of the brain network supporting spatial cognition. To address this issue, we applied a lesion mapping approach to the clinical phenomenon of topographical disorientation. Topographical disorientation is the inability to maintain accurate knowledge about the physical environment and use it for navigation. A review of published topographical disorientation cases identified 65 different lesion sites. Our lesion mapping analysis yielded a topographical disorientation brain map encompassing the classic regions of the navigation network: medial parietal, medial temporal, and temporo-parietal cortices. We also identified a ventromedial region of the prefrontal cortex, which has been absent from prior descriptions of this network. Moreover, we revealed that the regions mapped are correlated with the Default Mode Network sub-network C. Taken together, this study provides causal evidence for the distribution of the spatial cognitive system, demarking the major components and identifying novel regions.
Effectiveness and safety of stag beetle knife (SB knife) in management of Zenker’s diverticulum: a systematic review and meta-analysis
Authors: Dahiya Dushyant Singh , Deliwala Smit , Chandan Saurabh , Ramai Daryl , Ali Hassam , Kassab Lena L , Facciorusso Antonio , Kochhar Gursimran S
Published: December 2023

Stag Beetle Knife (SB Knife) is increasingly being utilized for Zenker’s Diverticulectomy (ZD). Our study assessed the effectiveness and safety of the SB Knife for the management of ZD. Ovid EBM reviews, Ovid Embase, Ovid Medline, ClinicalTrials.gov, Scopus, and Web of Science were searched to identify studies that utilized SB knife for ZD. Pooled proportions (PP) were calculated using the random-effects model. Heterogeneity was evaluated using I2 statistics. A total of 7 studies with 268 patients were included in the final analysis. Dysphagia and regurgitation were the most common clinical symptoms. The mean size of the ZD was 2.8 ± 0.7 cm and 28 (of 148) patients had undergone previous treatments. The PP of technical success was 98% (95% CI: 92.3–99.5; I20) with a mean procedure duration of 26.2 ± 8.3 minutes. The PP of clinical response at first follow-up and relapse after index procedure was 87.9% (95% CI: 81.6–92.3; I219) and 13.5% (95% CI: 9.6–18.6; I22), respectively. At final follow-up, the PP of clinical remission was 96.2% (95% CI: 91–98.4; I230.6) while the PP of procedure failure was 3.6% (95% CI: 1.6–8.1; I20). No severe adverse events (AEs) were noted while using the SB Knife. However, the PP of intraprocedural and postprocedural AEs was 13.2% (95% CI: 9.6–17.8; I20) and 9.3% (95% CI: 5.7–14.9; I2 < 20.9), respectively. SB Knife is highly safe and effective for Zenker’s Diverticulectomy with a failure rate of only 3.6%.
Implementation of climate adaptation in the public health sector in Europe: qualitative thematic analysis
Authors: Turner Grace A , de’Donato Francesca , Hoeben Annechien D , Nordeng Zuzana , Coleman Samantha , Otto Ilona M , Hajat Shakoor , Kovats Sari
Published: December 2023

Background

Adaptation, to reduce the health impacts of climate change, is driven by political action, public support and events (extreme weather). National adaptation policies or strategies are limited in addressing human health risks and implementation of adaptation in the public health community is not well understood.

Aim

To identify key issues in climate change adaptation implementation for public health in Europe.

Methods

Key informant interviews with decision-makers in international, national and local city governments in 19 European countries. Participants were recruited if a senior decision-maker working in public health, environmental health or climate adaptation.

Interviews addressed

Barriers and levers for adaptation, policy alignment, networks and evidence needs.

Results

Thirty-two interviews were completed between June and October 2021 with 4 international, 5 national and 23 city/local government stakeholders. Respondents reported inadequate resources (funding, training and personnel) for health-adaptation implementation and the marginal role of health in adaptation policy. A clear mandate to act was key for implementation and resource allocation. Limited cross-departmental collaboration and poor understanding of the role of public health in climate policy were barriers to implementation.

Conclusions

Across Europe, progress is varied in implementation of climate adaptation in public health planning. Providing appropriate resources, training, knowledge mobilization and supporting cross-departmental collaboration and multi-level governance will facilitate adaptation to protect human health.
An unbiased approach of molecular characterization of the endometrium: toward defining endometrial-based infertility
Authors: Bui Bich Ngoc , Ardisasmita Arif Ibrahim , Kuijk Ewart , Altmäe Signe , Steba Gaby , Mackens Shari , Fuchs Sabine , Broekmans Frank , Nieuwenhuis Edward
Published: December 2023

Infertility is a complex condition affecting millions of couples worldwide. The current definition of infertility, based on clinical criteria, fails to account for the molecular and cellular changes that may occur during the development of infertility. Recent advancements in sequencing technology and single-cell analysis offer new opportunities to gain a deeper understanding of these changes. The endometrium has a potential role in infertility and has been extensively studied to identify gene expression profiles associated with (impaired) endometrial receptivity. However, limited overlap among studies hampers the identification of relevant downstream pathways that could play a role in the development of endometrial-related infertility. To address these challenges, we propose sequencing the endometrial transcriptome of healthy and infertile women at the single-cell level to consistently identify molecular signatures. Establishing consensus on physiological patterns in endometrial samples can aid in identifying deviations in infertile patients. A similar strategy has been used with great success in cancer research. However, large collaborative initiatives, international uniform protocols of sample collection and processing are crucial to ensure reliability and reproducibility. Overall, the proposed approach holds promise for an objective and accurate classification of endometrial-based infertility and has the potential to improve diagnosis and treatment outcomes.
tRNA shape is an identity element for an archaeal pyrrolysyl-tRNA synthetase from the human gut
Authors: Krahn Natalie , Zhang Jingji , Melnikov Sergey V , Tharp Jeffery M , Villa Alessandra , Patel Armaan , Howard Rebecca J , Gabir Haben , Patel Trushar R , Stetefeld Jörg , Puglisi Joseph , Söll Dieter
Published: December 2023

Protein translation is orchestrated through tRNA aminoacylation and ribosomal elongation. Among the highly conserved structure of tRNAs, they have distinguishing features which promote interaction with their cognate aminoacyl tRNA synthetase (aaRS). These key features are referred to as identity elements. In our study, we investigated the tRNA:aaRS pair that installs the 22nd amino acid, pyrrolysine (tRNAPyl:PylRS). Pyrrolysyl-tRNA synthetases (PylRSs) are naturally encoded in some archaeal and bacterial genomes to acylate tRNAPyl with pyrrolysine. Their large amino acid binding pocket and poor recognition of the tRNA anticodon have been instrumental in incorporating >200 noncanonical amino acids. PylRS enzymes can be divided into three classes based on their genomic structure. Two classes contain both an N-terminal and C-terminal domain, however the third class (ΔpylSn) lacks the N-terminal domain. In this study we explored the tRNA identity elements for a ΔpylSn tRNAPyl from Candidatus Methanomethylophilus alvus which drives the orthogonality seen with its cognate PylRS (MaPylRS). From aminoacylation and translation assays we identified five key elements in ΔpylSn tRNAPyl necessary for MaPylRS activity. The absence of a base (position 8) and a G–U wobble pair (G28:U42) were found to affect the high-resolution structure of the tRNA, while molecular dynamic simulations led us to acknowledge the rigidity imparted from the G–C base pairs (G3:C70 and G5:C68).
A Case of Sustained Viral Shedding of Mpox With Ocular Involvement Resulting in Vision Loss
Authors: Speiser Lisa J , Wonnaparhown Alex M , Blair Janis , Shah Ami , Patel Dharmendra R , McCullough Ann E , Nicolasora Nelson , Khalsa Ann M , Orenstein Robert , Vikram Holenarasipur R , Huang Vivian , Seville Maria Teresa
Published: December 2023

Mpox, caused by infection with Monkeypox virus, usually presents as a mild, self-limited illness in immunocompetent persons that resolves within 2–4 weeks. Serious complications have been reported when mpox lesions involve vulnerable anatomic sites, such as the eye, and in those with substantial immunosuppression. We describe a patient with advanced human immunodeficiency virus infection and sustained viral shedding of mpox with ocular involvement, which resulted in vision loss.
Common variable immunodeficiency disorder-related liver disease is common and results in portal hypertension and an increased risk of death
Authors: Halliday Neil , Eden Nadia , Somers Henry , Burke Niall , Silva Hiroshi , Brito Camila GX , Hall Andrew , Quaglia Alberto , Burns Siobhan O. , Lowe David M. , Thorburn Douglas
Published: December 2023

Background:

Common variable immunodeficiency disorder (CVID) manifests with recurrent infections and inflammatory complications, including liver disease. We report the clinical features, natural history, and outcomes of patients with CVID-related liver disease (CVID-rLD) from a tertiary immunology and hepatology center.

Methods:

Two hundred eighteen patients were identified; CVID-rLD was defined by persistently abnormal liver function tests or evidence of chronic liver disease (CLD) or portal hypertension (PHTN) by radiological or endoscopic investigation, after exclusion of other causes. Patients with CVID-rLD were investigated and managed following a joint pathway between immunology and hepatology services. Data, including clinical parameters, investigations, and outcomes, were retrospectively collected.

Results:

A total of 91/218 (42%) patients had evidence of CVID-rLD, and 40/91 (44%) had PHTN. Patients with CVID-rLD were more likely to have other noninfectious complications of CVID (85/91, 93.4% vs. 75/127, 59.1%, p<0.001) including interstitial lung disease, gut disease, and autoimmune cytopenias. Nodular regenerative hyperplasia (NRH) was identified in 63.8% of liver biopsies, and fibrosis in 95.3%. Liver stiffness measurements (LSMs) were frequently elevated (median 9.95 kPa), and elevated LSM was associated with PHTN. All-cause mortality was higher in those with CVID-rLD (24/91, 26.4% vs. 14/127, 11%, p=0.003), which was the only organ complication associated with mortality (HR 2.24, 1.06–4.74, p=0.04). Factors predicting mortality in CVID-rLD included PHTN, increasing fibrosis, and LSM.

Conclusions:

Liver disease is a common complication of CVID as part of complex, multi-organ involvement and is associated with high rates of PHTN and an increased hazard of mortality.
Children Hospitalized With Respiratory Syncytial Virus Infection: A Pre Versus Late COVID-19 Pandemic Comparison
Authors: Solus Astrid , Huet Frederic , Perez-Martin Stephanie , Verney Cindy , Auvray Christelle , Binquet Christine , Piroth Lionel , Blot Mathieu
Published: December 2023

Our study aimed to compare children under 5 years hospitalized with respiratory syncytial virus in prepandemic and late-pandemic periods. We included 209 children at the Dijon University Hospital (France). We observed a nearly 3-fold increase in the number of cases in the late period, with older children, but less frequently requiring intensive care. These observations could help prepare a new pandemic.
Recurrent stroke shortly after mechanical thrombectomy secondary to carotid web: A case report
Authors: Yang Guo-Mei , Zhang Ren-Wei , Li Hua-Gang , Liu Yu-Min
Published: December 2023

Rationale:

Carotid web, a known source of thrombus for embolic stroke, presents a considerable risk of stroke recurrence. While case reports have demonstrated the safety and effectiveness of mechanical thrombectomy in treating carotid web-related stroke, the need for concurrent carotid artery stenting to prevent recurrent stroke immediately after thrombectomy remains unclear. This study aims to underscore the importance of immediate carotid artery stenting in preventing recurrent stroke following mechanical thrombectomy in patients with carotid web-related stroke.

Patient concerns:

A 43-year-old woman with acute onset of left limb weakness and slurred speech within 3 hours was admitted to the emergency department.

Diagnoses:

Computed tomographic angiography confirmed the M1 segment occlusion of the right middle cerebral artery.

Interventions:

The patient received intravenous thrombolysis in the local hospital and mechanical thrombectomy in our stroke center.

Outcomes:

Three days post-mechanical thrombectomy, there was a sudden exacerbation of her neurological deficit symptoms. A reexamination via computed tomographic angiography revealed a re-occlusion in M1 segment of the right middle cerebral artery, despite the implementation of stringent anticoagulation therapy for carotid web-related stroke.

Lessons:

Stroke patients with carotid web had a high risk of stroke recurrence and it was necessary to conduct carotid artery stenting to prevent stroke recurrence secondary to the carotid web immediately after mechanical thrombectomy.
Primary hepatic lymphoma a case report and literature review
Authors: Jiang Minzhi , Jiang Shudian , Yang Yu , Yao Rucheng , Hu Mingzheng
Published: December 2023

Rationale:

Primary hepatic lymphoma is a rare extranodal non-Hodgkin lymphoma that is primarily localized in the liver. It predominantly affects elderly males and presents with nonspecific laboratory findings, imaging results, and clinical symptoms, making diagnosis challenging. Histopathological examination serves as the gold standard for diagnosis, and treatment options include chemotherapy or surgical intervention combined with chemotherapy.

Patient concerns:

A 50-year-old male patient came to our hospital for treatment after finding a mass in his liver.

Diagnoses:

Laboratory tests and clinical symptoms lack specificity for primary hepatic lymphoma, and imaging findings can be difficult to differentiate. Pathology is the gold standard.

Outcomes:

The patient was dead.

Conclusion:

A definitive diagnosis primarily relies on histopathological examination, and surgical resection combined with chemotherapy yields better treatment outcomes.
Chronic kidney disease on the background of bardet–biedl syndrome: a case report and review of literature
Authors: Pokharel Pashupati , Pandey Uday , Sedai Samir , Khanal Kapil , Shrestha Midhan
Published: December 2023

Introduction:

Bardet–Biedl syndrome (BBS) is a rare autosomal recessive multisystem disorder characterized by retinal dystrophy, obesity, postaxial polydactyly, renal dysfunction, learning difficulties, and hypogonadism. In this case report, the authors present the clinical course and management of a patient with BBS who developed chronic kidney disease (CKD).

Case presentation:

An 18-year-old male presented to the emergency department with chief complaints of fever, cough, vomiting, and decreased urine output for 7 days. Parents complained that the child had a delay in development compared to other children of the same age group. On examination, the patient had tachypnea, periorbital and pedal edema, expiratory wheeze with bilateral basal crackles, polydactyly, central obesity, microtestes, and delayed developmental milestones. Ultrasonography revealed bilateral small kidneys with increased cortical echotexture and loss of corticomedullary differentiation. Based on clinical features, the patient was diagnosed with CKD in the background of BBS. Hemodialysis was initiated after the diagnosis.

Discussion:

The management of CKD in the background of BBS poses unique challenges due to the complex multisystem involvement of this genetic disorder. There should be early reorganization and management of this condition so that the patient can have a better quality of life. Moreover, in developing countries like Nepal, genetic testing and diagnosis should be made easily accessible for better patient outcome.

Conclusion:

Multidisciplinary approach involving nephrologists, ophthalmologists, endocrinologists, and geneticists is important to optimize the treatment and long-term management of Badet Biedel patients.
Usefulness of the hybrid technique of interventional radiology and endoscopic treatment for intestinal bleeding after pancreaticoduodenectomy: a case report
Authors: Chiba Nobutaka , Nomura Yuri , Mizuochi Minori , Sato Jun , Saito Takeshi , Sakurai Atsushi , Kinoshita Kosaku
Published: December 2023

Introduction and importance:

In endovascular treatment of ruptured pseudoaneurysm after pancreaticoduodenectomy (PD) with gastrointestinal bleeding, treatment for vasospasm of the culprit vessel from haemorrhagic shock and subsequent reperfusion has not been determined before.

Case presentation:

The authors hereby present you with a case of a 59-year-old man with unknown operative method upon arrival at the Emergecy room and who had hematemesis and collapse 6 months post-PD surgery.

Clinical discussion:

An initial contrast-enhanced computed tomography (CT) revealed no obvious source of bleeding, so an upper gastrointestinal endoscope was performed. Rebleeding occurred during the examination, and interventional radiology was performed because haemostasis was difficult. Coil embolization was performed for leakage of contrast material from the gastroduodenal artery stump into the gastrointestinal tract. However, because the embolization was uncertain due to vasospasm of the common hepatic artery, endoscopic clipping of the perforation site was also performed to prevent rebleeding due to reperfusion after improvement of vasospasm. A CT scan 5 days later showed reperfusion of the coil-implanted vessel. No rebleeding or hepatic infarction occurred postoperatively.

Conclusion:

In this case, the haemostasis by coil embolization was uncertain due to the presence of vasospasm, and clipping was used in combination with the procedure to prevent rebleeding.
Clustering of >145,000 Symptom Logs Reveals Distinct Pre, Peri, and Post Menopausal Phenotypes
Authors: Aras Shravan G. , Grant Azure D. , Konhilas John P.
Published: December 2023

Background and Objectives

The transition to menopause is commonly associated with disappearance of menstrual cycle symptoms and emergence of vasomotor symptoms. Although menopausal women report a variety of mood, digestive, and pain symptoms, it remains unclear what symptoms emerge prior to menopause, if symptoms occur in predictable clusters, how these clusters change from across the premenopause-perimenopause-menopause transition, or if distinct phenotypes are present within each life stage.

Methods

We present analysis of self-reported symptom presentation in premenopausal to menopausal women using the MenoLife app, which includes 4,789 (n=1,115(23%) premenopausal, n=1,388(29%) perimenopausal, n=2,286(48%) menopausal) individuals and 147,501 (n=27,371(19%) premenopausal, n=57,964(39%) perimenopausal, n=61,806(42%) menopausal) symptom logs. Clusters generated from logs of 45 different symptoms were assessed for similarities across methods: hierarchical clustering analysis (HCA), K-Means clustering of principal components of symptom reporting, and binomial network analysis. Participants were further evaluated based on menstrual cycle regularity or type of menopause.

Results

Menstrual cycle-associated symptoms (e.g., cramps, breast swelling), digestive, mood, and integumentary symptoms were characteristic of premenopausal women. Vasomotor symptoms, pain, mood, and cognitive symptoms were characteristic of menopause. Perimenopausal women exhibited both menstrual cycle-associated and vasomotor symptoms. Subpopulations across life stages presented with additional correlated mood and cognitive symptoms, integumentary complaints, digestive, nervous, or sexual symptoms. Symptoms also differed among women depending on the reported regularity of their menstrual cycles or the way in which they entered menopause. Notably, we identified a set of symptoms that were very common across life stages: fatigue, headache, anxiety, and brain fog. We consistently identified the lack of predictive power of hot flashes for other symptoms except night sweats.

Conclusions

Together, premenopausal women exhibit menstrual cycle-associated symptoms and menopausal women reported vasomotor symptoms, perimenopausal women report both; and all report high rates of fatigue, headache, anxiety, and brain fog. Limiting focus of menopausal treatment to vasomotor symptoms, or to premenstrual syndrome in premenopausal women, neglects a large proportion of overall symptom burden. Future research and interventions targeting mood and cognitive, digestive, and integumentary symptoms are needed across stages of female reproductive life.
Real-World Performance of the Alinity m STI Assay for the simultaneous detection of Chlamydia trachomatis, Neisseria gonorrhea, Mycoplasma genitalium, and Trichomonas vaginalis in Clinical Specimens at a Large Tertiary Hospital System in the United States
Authors: Rexroth Karen C. , Kostera Joshua
Published: December 2023

Background

In the US, sexually transmitted infections (STI) are reported for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) but not Trichomonas vaginalis (TV) and Mycoplasma genitalium (MG). TV and MG surveillance data in the US remains inadequate. We evaluated the performance of the fully automated, multi-plex PCR-based Alinity m STI assay, to simultaneously detect CT, NG, TV, and MG, at a large Veterans Affairs hospital system.

Methods

260 urine, urogenital, and extragenital clinical specimens were tested with the Alinity m STI assay and the results were compared to those from the Abbott RealTime CT/NG assay in our lab and TV and MG assays run at an external reference laboratory.

Results

Alinity m STI assay results for urine specimens had an overall percent agreement (OPA) with the RealTime comparator assay of 187/187 (100.0%) for CT and 186/187 (99.5%) for NG. For 20 rectal specimens, the OPA for CT was 95% and for NG was 100%; for 13 oral specimens, OPA was 100% for CT and 92.3% for NG. Of the urine specimens sent for TV and MG testing, 100% agreement was observed between the Alinity m STI assay and TV (n=104) and MG (n=30) comparator assay results.

Conclusions

The Alinity m STI assay is an easy-to-use, sensitive and specific assay that allows high-throughput testing for common and undertested STI pathogens to facilitate surveillance efforts.

KEY MESSAGES

What is already known on this topic

Mycoplasma genitalium and Trichomonas vaginalis are sexually transmitted infections, however, global prevalence data vary between geographical regions, as these sexually transmitted infections are not included in routine screening.

What this study adds

This study aimed at assessing Trichomonas and Mycoplasma prevalence and association with a positive Chlamydia and/or Gonorrhoeae result.

How this study might affect research, practice, or policy

Including Mycoplasma genitalium and Trichomonas vaginalis testing in a routine screening STI diagnostic algorithm, with cost-effective and accurate multiplex assays can improve diagnosis to initiation of appropriate treatment.
Mechanical transapical coupling of endometrial epithelial cells during implantation
Authors: Sakurai Jun , Kinoshita Noriyuki , Otani Tetsuhisa , Koyama Hiroshi , Furuse Mikio , Fujimori Toshihiko
Published: December 2023

Epithelial cells lining the lumen of organs have an apical-basal polarity, and mechanical cell contacts are located in the lateral and basal regions. During early pregnancy in rodents, the luminal space of the uterus is closed, and opposing epithelial cells attach to each other at apical–apical surfaces. Here, we show that cells are mechanically coupled at the apical cell–cell contacts. The apical plasma membrane was intricately intertwined between opposing cells. Extracellular matrix and tight junction molecules were localized at apical contacts. Claudin inhibition resulted in impaired luminal closure, suggesting a functional requirement of claudins for the establishment of transapical coupling. The present results demonstrate a mechanical cell–cell interaction that occurs between apical–apical surfaces in addition to lateral and basal cell junctions.

One Sentence Summaries

Transapical coupling of epithelial cells mediated by extracellular matrix and tight junction molecules
Using twin-pairs to assess potential bias in polygenic prediction of externalising behaviours across development
Authors: Bright Joanna K. , Rayner Christopher , Freeman Ze , Zavos Helena M.S. , Ahmadzadeh Yasmin I. , Viding Essi , McAdams Tom A.
Published: December 2023

Prediction from polygenic scores may be confounded sources of passive gene-environment correlation (rGE; e.g. population stratification, assortative mating, and environmentally mediated effects of parental genotype on child phenotype). Using genomic data from 10,000 twin pairs, we asked whether polygenic scores from the recent externalising genome-wide association study predicted conduct problems, ADHD symptomology and callous-unemotional traits, and whether these predictions are biased by rGE. We ran regression models including within-family and between-family polygenic scores, to separate the direct genetic influence on a trait from environmental influences that correlate with genes (indirect genetic effects). Findings suggested that this externalising polygenic score is a good index of direct genetic influence on conduct and ADHD-related symptoms across development, with minimal bias from rGE, although the polygenic score predicted less variance in CU traits. Post-hoc analyses showed some indirect genetic effects acting on a common factor indexing stability of conduct problems across time and contexts.
DBF4, not DRF1, is the crucial regulator of CDC7 kinase at replication forks
Authors: Göder Anja , Maric Chrystelle , Rainey Michael D. , Cazzaniga Chiara , Shamavu Daniel , Cadoret Jean-Charles , Santocanale Corrado
Published: December 2023

In eukaryotes, CDC7 kinase is crucial for DNA replication initiation and has been involved in fork processing and replication stress response. Human CDC7 requires the binding of either one of two regulatory subunits, DBF4 and DRF1, for its activity. However, it is unclear whether the two regulatory subunits target CDC7 to a specific set of substrates, thus having different biological functions, or if they act redundantly.

Using genome editing technology, we generated an isogenic set of cell lines deficient in either one of the two CDC7-activating subunits: these cells are viable but present signs of genomic instability, indicating that both DBF4 and DRF1 can independently support CDC7 for bulk DNA replication. Nonetheless, DBF4-deficient cells show altered replication efficiency, including partial deficiency in MCM helicase phosphorylation and alterations in the replication timing of discrete genomic regions. Notably, we find that CDC7 function at replication forks is entirely dependent on DBF4 and not DRF1. Thus, DBF4 is the primary regulator of CDC7 activity, likely mediating most of its functions in unperturbed DNA replication and during replication fork processing upon replication interference.
IIHP: Intelligent Incident Hypertension Prediction in Obstructive Sleep Apnea
Authors: Halimi Milani Omid , Cetin Ahmet Enis , Prasad Bharati
Published: December 2023

The Obstructive sleep apnea (OSA) increases the risk of hypertension, mainly attributed to intermittent hypoxia and sleep fragmentation. Given the multifaceted pathogenesis of hypertension, accurately predicting incident hypertension in individuals with OSA has posed a considerable challenge. In this study, we leveraged Machine Learning (ML) techniques to develop a predictive model for incident hypertension up to five years after OSA diagnosis by polysomnography. We used data from the Sleep Heart Health Study (SHHS), which included 4,797 participants diagnosed with OSA. After excluding those with pre-existing hypertension and Apnea Hypopnea Index (AHI) values below 21 per hour, we had 671 participants with five-year follow-up data. We adopted two distinct methodologies. We first implemented adaptive convolution layers to extract features from the signals and combined them into a 2D array. The 2D array was further processed by a 2D pre-trained neural network to take advantage of transfer learning. Subsequently, we delved into feature extraction from full-length signals across various temporal frames, resulting in a 2D feature array. We studied the use of various 2D networks such as MobileNet, EfficientNet, and a family of RESNETs. The best algorithm achieved an average area under the curve of 72%. These results suggest a promising approach for predicting the risk of incident hypertension in individuals with OSA, providing tools for practice and public health initiatives.
Profile of tetralogy of Fallot at the cardiology clinic of Saint-Damien hospital from January 2019 to December 2021
Authors: Désir Naïka Paulemie , Isaac Julien Adonaï Aly , Alexandre Richcard , Fevry Joanne , Brice Taina , Noisette Alexandra
Published: December 2023

Objective

Our work aimed to study the epidemiological and clinical aspects of Tetralogy of Fallot (TF) in the cardiology unit of the Saint-Damien Nos Petits Frères et Sœurs hospital in Haiti.

Methodology

This is a retrospective study of patients aged 0 to 18 years with Tetralogy of Fallot confirmed by echocardiography. Data were entered using an elaborated form and analyzed with Epi Info software version 7.2.2.16 and Microsoft Excel 2013.

Results

From January 2019 to December 2021, we identified 102 patients aged 0 to 18 years with TF. A male predominance was noted with a sex ratio M/F of 1.55. The average age of discovery of our cohort was 3 years and 7 months [0-16 years; standard deviation: 9.9]. The clinical signs were dominated by a systolic murmur (91.18%) followed by cyanosis (39.22%) and dyspnea (33.33%). On echocardiography, the regular form (76.47%) associated with the severe stenosis (83.33%) was remarkable. 20.59% of patients were able to benefit from surgery and the mortality rate was 14.94%. Patients were presenting at an advanced stage where they mostly needed surgical treatment to survive.

Conclusion

This study shows that the prevalence of TF is also high in developing countries. The heart murmur at the pulmonary focus and the cyanosis were more present on physical examination. Patients were presenting at an advanced stage where they mostly needed surgical treatment to survive. Preventive measures are needed to reduce the mortality rate.
PVT in patients presenting with post-acute sequelae of COVID-19
Authors: Chakrabarti Shinjon , Krishnan Kamini , Galioto Rachel
Published: December 2023

We investigated performance validity tests (PVTs) in patients presenting with new onset cognitive complaints associated with post-acute sequelae of COVID-19 infection (PASC). Retrospective data were obtained from IRB-approved registries. All patients completed the Victoria Symptom Validity Test (VSVT) in conjunction with a neuropsychological evaluation. A sub-analysis included 7 other PVT measures. The PASC sample was compared to an analogous multiple sclerosis (MS) sample with known PVT failure rates. The PASC sample consisted of 177 patients (49.4 ± 11.2 years), educated (14.7 ± 2.3 years), predominantly female (81.4%), and white, non-Hispanic (85.3%) patients. Seven percent of the PASC sample scored below the established VSVT hard item cut-off, and of those with invalid VSVT over 50% failed 3 or more additional PVTs. In comparison to a MS sample, the PASC sample reported comparable psychological symptoms, but were significantly less likely to produce invalid VSVT scores and seek disability benefits. This study provides a profile of PVTs in patients presenting with PASC. The general infrequence of invalid responding in this PASC sample (7%) is noteworthy compared to an MS sample and highlights the role of additional factors in non-credible response such as elevated psychological symptoms or pursuit of disability.
Exploring the application of deep learning methods for polygenic risk score estimation
Authors: Squires Steven , Weedon Michael N. , Oram Richard A.
Published: December 2023

Background

Polygenic risk scores (PRS) summarise genetic information into a single number with multiple clinical and research uses. Machine learning (ML) has revolutionised a diverse set of fields, however, the impact of ML on genomics in general, and PRSs in particular, has been less significant. We explore how ML can improve the generation of PRSs.

Methods

We train ML models on known PRSs using UK Biobank data. We explore whether the models can recreate human programmed PRSs, including using a single model to generate multiple PRSs, and the difficulty in using ML for PRS generation. We also investigate how ML can compensate for missing data and the constraints on performance.

Results

We demonstrate almost perfect generation of PRSs, including when using one model to predict multiple scores, and with little loss of performance with reduced quantity of training data. For an example set of missing SNPs the MLP produces predictions that enable separation of cases from population samples with an area under the receiver operating characteristic curve of 0.847 (95% CI: 0.828-0.864) compared to 0.798 (95% CI: 0.779-0.818) for the PRS. We provide evidence that input information is the limiting factor of further improvement.

Conclusions

ML can accurately generate PRSs, including with one model for multiple PRSs. The models are transferable and have high longevity. With certain missing SNPs the ML models can statistically significantly improve on normal PRS generation. Models trained are probably at the edge of performance and further improvements likely require use of additional input data.

Code is available athttps://github.com/stevensquires/
Amalgam plays a dual role in controlling the number of leg muscle progenitors and regulating their interactions with developing tendon
Authors: Moucaud Blandine , Prince Elodie , Ragot Elia , Renaud Yoan , Jagla Krzysztof , Junion Guillaume , Soler Cedric
Published: December 2023

Formation of functional organs requires cell-cell communication between different cell lineages, and failure in this communication can result in severe developmental defects. Hundreds of possible interacting pairs of proteins are known, but identifying the interacting partners that ensure a specific interaction between two given cell types remains challenging. Here, we use the Drosophila leg model and our cell type-specific transcriptomic datasets to uncover the molecular mediators of cell-cell communication between tendon and muscle precursors. Through the analysis of gene expression signatures of appendicular muscle and tendon precursor cells, we identify two candidates for early interactions between these two cell populations: Amalgam (Ama) encoding a secreted protein and Neurotactin (Nrt) known to encode a membrane-bound protein. Developmental expression and function analyses reveal that: i) Ama is expressed in the leg myoblasts, whereas Nrt is expressed in adjacent tendon precursors, and ii) in Ama and Nrt mutants, myoblast-tendon cell-cell association is lost, leading to tendon developmental defects. Furthermore, we demonstrate that Ama acts downstream of the FGFR pathway to maintain the myoblast population by promoting cell survival and proliferation in a Nrt-independent manner. Together, our data pinpoint Ama and Nrt as molecular actors ensuring early reciprocal communication between leg muscle and tendon precursors, a prerequisite for the coordinated development of the appendicular musculoskeletal system.
Gain efficiency with streamlined and automated data processing: Examples from high-throughput monoclonal antibody production
Authors: Kotowicz Malwina , Fengler Sven , Kurkowsky Birgit , Meyer-Berhorn Anja , Moretti Elisa , Blersch Josephine , Shumanska Magdalena , Schmidt Gisela , Kreye Jakob , van Hoof Scott , Sánchez-Sendín Elisa , Reincke S. Momsen , Krüger Lars , Prüss Harald , Denner Philip , Fava Eugenio , Stappert Dominik
Published: December 2023

Data management and sample tracking in complex biological workflows are essential steps to ensure necessary documentation and guarantee the reusability of data and metadata. Currently, these steps pose challenges related to correct annotation and labeling, error detection, and safeguarding the quality of documentation. With growing acquisition of biological data and the expanding automatization of laboratory workflows, manual processing of samples is no longer favorable, as it is time- and resource-consuming, is prone to biases and errors, and lacks scalability and standardization. Thus, managing heterogeneous biological data calls for efficient and tailored systems, especially in laboratories run by biologists with limited computational expertise. Here, we showcase how to meet these challenges with a modular pipeline for data processing, facilitating the complex production of monoclonal antibodies from single B-cells. We present best practices for development of data processing pipelines concerned with extensive acquisition of biological data that undergoes continuous manipulation and analysis. Moreover, we assess the versatility of proposed design principles through a proof-of-concept data processing pipeline for automated induced pluripotent stem cell culture and differentiation. We show that our approach streamlines data management operations, speeds up experimental cycles and leads to enhanced reproducibility. Finally, adhering to the presented guidelines will promote compliance with FAIR principles upon publishing.