bluuebunny/crossref_metadata_2025 huggingface dataset:
Airline revenue management with segmented continuous pricing: methods and competitive effects
Authors: Long Yanbin , Belobaba Peter
Published: December 2023

With the introduction of IATA’s New Distribution Capability (NDC), airlines will no longer be limited to discrete fare classes for their fare product distribution but could show fare quotes from continuous ranges to booking requests. NDC will also allow airlines to present different fare quotes to passengers from different demand segments as identified by the airline. In theory, airlines can better extract passenger willingness to pay, and thus, see gains in revenue, by offering segmented continuous fare quotes to different passengers requesting to book. This paper describes the revenue management (RM) methods for Segmented Continuous Pricing and examines their potential effects on airlines’ revenue through simulations in the Passenger Origin–Destination Simulator (PODS). We describe a class-based algorithm for continuous pricing, a straightforward extension from the traditional methods used with existing RM systems. Our simulation results show that in a calibrated scenario in which only one airline adopts Segmented Continuous Pricing and has an 80% accuracy in identifying business versus leisure passenger booking requests, the first-mover airline can see as much as a 17% revenue gain, at the expense of competitors. The revenue gains come primarily from the leisure passenger segment by offering lower fares than competitors closer to departure. The first-mover airline loses bookings but does not see losses in revenue from the business passenger segment. We also explore potential response strategies by the competing airlines. We discover that competitors can reverse the first-mover’s revenue gain by removing their fare restrictions while still using traditional RM methods. We conclude that although adopting Segmented Continuous Pricing is promising in theory, its gains in practice will depend heavily on the competitive situation and the responses made by competing airlines.
The reaction of wild-caught northern brown bandicoots (Isoodon macrourus) to predators
Authors: Edwards M. C. , Hoy J. M. , FitzGibbon S. I. , Murray P. J.
Published: December 2023

Australia’s mammals are facing devastating effects from introduced predators such as cats and foxes. It is hypothesised that this may be because Australian mammals do not recognise some predators and are naïve to the threat they pose. We tested how wild-caught northern brown bandicoots (Isoodon macrourus) reacted to a variety of predators and their cues in captivity. These cues were live predators, taxidermied predators and predator faeces. Bandicoots spent less time feeding and took longer to begin feeding in the presence of a live dog. However, they did not display a significant difference in behaviours in the presence of any other predator cue when compared with the baseline. This suggests that bandicoots may perceive live dogs as a threat, and that the use of taxidermied predators and predator faeces may not elicit avoidance behaviours in bandicoots. Bandicoots may need to be trained to recognise and respond appropriately to some predator cues to maximise their chance of survival.
Post-Hyaluronic Acid Recurrent Eyelid Edema: Pathophysiologic Mechanisms and a Proposed Treatment Protocol
Authors: Karlin Justin , Vranis Neil , Dayan Erez , Parsa Kami
Published: December 2023

Background

Hyaluronic acid (HA) filler injections for facial augmentation are commonly administered but can lead to post-hyaluronic acid recurrent eyelid edema (PHAREE). The pathophysiology of this condition has not been fully understood.

Objectives

To report the successful treatment of PHAREE using serial hyaluronidase and fractionated radiofrequency microneedling, with additional carbon dioxide laser skin resurfacing in selected patients.

Methods

Five patients with PHAREE were treated with serial hyaluronidase injections and fractionated radiofrequency microneedling, with 2 patients receiving carbon dioxide laser treatment. The patients were followed up for a minimum of 24 months.

Results

All patients reported a resolution of PHAREE signs/symptoms with no adverse effects or recurrence. One patient demonstrated complete resolution after a single treatment; 4 required a series of treatments.

Conclusions

The proposed treatment protocol may provide advantages over hyaluronidase alone for PHAREE. The impermeable malar septum, vulnerable eyelid lymphatics, and potential immunogenicity of HA fragments likely contribute to PHAREE pathophysiology. Further research on pathophysiologic mechanisms is warranted.

Level of Evidence: 4
Deep learning from atrioventricular plane displacement in patients with Takotsubo syndrome: lighting up the black-box
Authors: Zaman Fahim , Isom Nicholas , Chang Amanda , Wang Yi Grace , Abdelhamid Ahmed , Khan Arooj , Makan Majesh , Abdelghany Mahmoud , Wu Xiaodong , Liu Kan
Published: December 2023

Aims

The spatiotemporal deep convolutional neural network (DCNN) helps reduce echocardiographic readers’ erroneous ‘judgement calls’ on Takotsubo syndrome (TTS). The aim of this study was to improve the interpretability of the spatiotemporal DCNN to discover latent imaging features associated with causative TTS pathophysiology.

Methods and results

We applied gradient-weighted class activation mapping analysis to visualize an established spatiotemporal DCNN based on the echocardiographic videos to differentiate TTS (150 patients) from anterior wall ST-segment elevation myocardial infarction (STEMI, 150 patients). Forty-eight human expert readers interpreted the same echocardiographic videos and prioritized the regions of interest on myocardium for the differentiation. Based on visualization results, we completed optical flow measurement, myocardial strain, and Doppler/tissue Doppler echocardiography studies to investigate regional myocardial temporal dynamics and diastology. While human readers’ visualization predominantly focused on the apex of the heart in TTS patients, the DCNN temporal arm’s saliency visualization was attentive on the base of the heart, particularly at the atrioventricular (AV) plane. Compared with STEMI patients, TTS patients consistently showed weaker peak longitudinal displacement (in pixels) in the basal inferoseptal (systolic: 2.15 ± 1.41 vs. 3.10 ± 1.66, P < 0.001; diastolic: 2.36 ± 1.71 vs. 2.97 ± 1.69, P = 0.004) and basal anterolateral (systolic: 2.70 ± 1.96 vs. 3.44 ± 2.13, P = 0.003; diastolic: 2.73 ± 1.70 vs. 3.45 ± 2.20, P = 0.002) segments, and worse longitudinal myocardial strain in the basal inferoseptal (−8.5 ± 3.8% vs. −9.9 ± 4.1%, P = 0.013) and basal anterolateral (−8.6 ± 4.2% vs. −10.4 ± 4.1%, P = 0.006) segments. Meanwhile, TTS patients showed worse diastolic mechanics than STEMI patients (Eʹ/septal: 5.1 ± 1.2 cm/s vs. 6.3 ± 1.5 cm/s, P < 0.001; Sʹ/septal: 5.8 ± 1.3 cm/s vs. 6.8 ± 1.4 cm/s, P < 0.001; Eʹ/lateral: 6.0 ± 1.4 cm/s vs. 7.9 ± 1.6 cm/s, P < 0.001; Sʹ/lateral: 6.3 ± 1.4 cm/s vs. 7.3 ± 1.5 cm/s, P < 0.001; E/Eʹ: 15.5 ± 5.6 vs. 12.5 ± 3.5, P < 0.001).

Conclusion

The spatiotemporal DCNN saliency visualization helps identify the pattern of myocardial temporal dynamics and navigates the quantification of regional myocardial mechanics. Reduced AV plane displacement in TTS patients likely correlates with impaired diastolic mechanics.
Pharmacogenetic Variation in Neanderthals and Denisovans and Implications for Human Health and Response to Medications
Authors: Wroblewski Tadeusz H , Witt Kelsey E , Lee Seung-been , Malhi Ripan S , Peede David , Huerta-Sánchez Emilia , Villanea Fernando A , Claw Katrina G
Published: December 2023

Modern humans carry both Neanderthal and Denisovan (archaic) genome elements that are part of the human gene pool and affect the life and health of living individuals. The impact of archaic DNA may be particularly evident in pharmacogenes—genes responsible for the processing of exogenous substances such as food, pollutants, and medications—as these can relate to changing environmental effects, and beneficial variants may have been retained as modern humans encountered new environments. However, the health implications and contribution of archaic ancestry in pharmacogenes of modern humans remain understudied. Here, we explore 11 key cytochrome P450 genes (CYP450) involved in 75% of all drug metabolizing reactions in three Neanderthal and one Denisovan individuals and examine archaic introgression in modern human populations. We infer the metabolizing efficiency of these 11 CYP450 genes in archaic individuals and find important predicted phenotypic differences relative to modern human variants. We identify several single nucleotide variants shared between archaic and modern humans in each gene, including some potentially function-altering mutations in archaic CYP450 genes, which may result in altered metabolism in living people carrying these variants. We also identified several variants in the archaic CYP450 genes that are novel and unique to archaic humans as well as one gene, CYP2B6, that shows evidence for a gene duplication found only in Neanderthals and modern Africans. Finally, we highlight CYP2A6, CYP2C9, and CYP2J2, genes which show evidence for archaic introgression into modern humans and posit evolutionary hypotheses that explain their allele frequencies in modern populations.
Differences in olfactory functional connectivity in early-onset depression and late-onset depression
Authors: Chen Ben , Yang Mingfeng , Liu Meiling , Wang Qiang , Zhou Huarong , Zhang Min , Hou Le , Wu Zhangying , Zhang Si , Lin Gaohong , Zhong Xiaomei , Ning Yuping
Published: December 2023

Background

Late-onset depression (LOD) and early-onset depression (EOD) exhibit different pathological mechanisms and clinical phenotypes, including different extents of olfactory dysfunction. However, the brain abnormalities underlying the differences in olfactory dysfunction between EOD and LOD remain unclear.

Objective

The aim of this study was to compare the functional connectivity (FC) patterns of olfactory regions between EOD patients and LOD patients and examine their relationship with cognitive function.

Methods

One hundred and five patients with EOD, 101 patients with LOD and 160 normal controls (NCs) were recruited for the present study. Participants underwent clinical assessment, olfactory testing, cognitive assessments, and magnetic resonance imaging. Eight regions of the primary and secondary olfactory regions were selected to investigate olfactory FC.

Results

Patients with LOD exhibited decreased odor identification (OI) compared with patients with EOD and NCs. The LOD group exhibited decreased FC compared with the EOD and NC groups when primary and secondary olfactory regions were selected as the regions of interest (the piriform cortex, lateral entorhinal cortex, and orbital-frontal cortex). Additionally, these abnormal olfactory FCs were associated with decreased cognitive function scores and OI, and the FC between the left orbital-frontal cortex and left amygdala was a partial mediator of the relationship between global cognitive scores and OI.

Conclusion

Overall, patients with LOD exhibited decreased FC in both the primary and secondary olfactory cortices compared with patients with EOD, and abnormal olfactory FC was associated with OI dysfunction and cognitive impairment. The FC between the orbital-frontal cortex and amygdala mediated the relationship between global cognitive function and OI.
PERCHING syndrome caused by variant gene KLHL7 in the first Iranian patient: a case report study
Authors: Ghelichi-Ghojogh Mousa , Golfiroozi Saeed , Delavari Sahar , Hosseini Seyed Ahmad
Published: December 2023

Introduction and importance:

PERCHING syndrome is a condition that affects many parts of the body and is caused by genes passed down from both parents. People with this syndrome have delays in their development, unusual facial features, trouble eating and breathing, slow overall growth, weak muscles, and stiff joints.

Case presentation:

The child at the age of 6 months suffered from developmental delay, delayed walking, speech delay, and hypotonia and was referred to the Neurologist. Also, he has an abnormal phenotype. Whole-exome sequencing (WES) revealed a missense variant in the KLHL7 gene at a highly conserved genomic Chr7: 23124718T>G; NM_018846:exon3:c.110T>G:p.Val37Gly.

Clinical discussion:

One way to explain the difference in physical characteristics caused by recessive KLHL7 mutations might be related to the person’s genetic makeup. However, the genes someone has do not always accurately determine their physical traits.

Conclusion:

This report will help us learn more about the different traits and characteristics of Perching syndrome. The authors need to do more research on how proteins work and study more about patients with different characteristics to fully understand this.
Exosomes-mediated drug delivery for the treatment of myocardial injury
Authors: Li Jiang , Lin Aiqin , Jiang Rui , Chen Pingping , Xu Chengyang , Hou Yuanyuan
Published: December 2023

Cardiovascular disease has become a major cause of death worldwide. Myocardial injury (MI) caused by myocardial infarction, myocarditis, and drug overdose can lead to impaired cardiac function, culminating in serious consequences such as angina pectoris, arrhythmias, and heart failure. Exosomes exhibit high biocompatibility and target specificity, rendering them an important non-cellular therapy for improving MI. Exosomes are diminutive vesicles that encapsulate nucleic acids and proteins. Exosomes derived from cardiac stem cells themselves have therapeutic effects, and they can also serve as carriers to deliver therapeutic drugs to recipient cells, thereby exerting a therapeutic effect. The molecules within exosomes are encapsulated in a lipid bilayer, allowing them to stably exist in body fluids without being affected by nucleases. Therefore, the utilization of exosomes as drug delivery systems (DDS) for disease treatment has been extensively investigated and is currently undergoing clinical trials. This review summarizes the therapeutic effects of exosomes on MI and provides an overview of current research progress on their use as DDS in MI.
Vascular trauma injury evaluation in Khorramabad, Iran: a cross-sectional study
Authors: Sharifian Masoud , Marzban Atefeh , Beiranvand Mania , Mahboubi Mohammad Javad , Garshasebi Mohammad
Published: December 2023

Background:

Vascular trauma injuries are associated significantly with disabilities and mortality where prompt diagnosis and management are of great importance.

Objectives:

In this study, the authors aim to evaluate the pattern of vascular trauma injuries.

Methods:

This descriptive retrospective study was performed on patients with vascular injuries due to trauma referred to (Shohada Ashayer Hospital and Shahid Chamran Hospital, Khorramabad). Patients’ files were evaluated for the following data: diagnostics, types of treatment and outcome, type of trauma, cause of trauma, anatomy of the injured site, duration of surgery, type of lesion, delayed complication, and requirement of revision surgery. The data obtained were descriptively evaluated using SPSSv22.

Results:

Of 233 patients studied, 95.3% were males. The mean age of the patients was 29.15±11.8 years. 82.8% of patients presented with penetrating trauma whereas 32.2% of patients had stab wound trauma. The most common sign at the time of referral was a loss of sensation in 54.9% of patients. Direct diagnosis based on clinical presentation was made in 79% of patients. The upper extremity was the most common site of vascular injury in 77.3% of patients with the involvement of radial and ulnar arteries, in 63.1%. 66.9% of patients underwent primary vascular repair, 92 received revision surgery, and 69 required blood transfusion.

Conclusion:

Epidemiological studies of vascular injury can help clinicians and local healthcare centres to understand the pattern of vascular trauma based on the geographical location and train trauma surgeons and medical staff to provide effective and timely management.
Endovascular treatment of subdural haematoma in patient under anti-platelet therapy: a case report
Authors: Thapa Paras , Bhattarai Ganesh , Kharel Santosh Kumar , Kunwar Pratiksha , Bhandari Sagar , Bhandari Shailaj , Shilpakar Sushil , Thapa Bikash , Thapa Ajit , Sharma Mohan Raj
Published: December 2023

Introduction:

The incidence of chronic subdural haematoma (cSDH) is relatively high among the elderly population. Other known risk factors for cSDH include male sex, dependency on anti-platelet or anticoagulant medication, and chronic alcoholism. Although, the standard mode of treatment for cSDH is surgery, embolization of the middle meningeal artery (MMA), either upfront or as an adjunct to surgical evacuation can be used for the treatment of cSDH.

Case presentation:

The authors present a case of a 75-year-old female with prior history of posterior-lateral wall myocardial infarction (MI) eight years back presented to our centre with the chief complaints of a gradual onset of cough and headache for 2 months. The patient had no history of trauma, loss of consciousness, seizures, and vomiting. There was no history of diabetes, hypertension, pulmonary tuberculosis, and other chronic illness.

Discussion:

The concurrent use of anti- platelet drug during a surgical procedure can make the treatment challenging. Endovascular treatment can be a primary treatment modality in such situation.

Conclusion:

Elimination of blood supply by middle meningeal artery embolization is emerging as a safe, minimally invasive alternative to treat cSDH.
Ergonomics in the operation-theatre: a healthcare provider-based cross-sectional study
Authors: Shrestha Oshan , Basukala Sunil , Thapa Niranjan , Karki Sagun , Shrestha Lochan , Shrestha Melina , Mehta Bipin Kumar , Sunuwar Bikesh Raj , Maharjan Pujan
Published: December 2023

Background:

Performing surgery is a task that demands mental stability, precision, and vigilant eyes, along with resilient physical strength, as surgeons and those who assist the surgeons have to assume a sustained, difficult posture that can go on for hours. About 23–100% of surgeons report musculoskeletal discomfort that originates from poor ergonomics.

Methods:

Ethical clearance for the study was obtained. This cross-sectional study, conducted in a tertiary centre among the healthcare providers working inside the operating room, spanned from 1 March 2023, to 26 June 2023. Systematic sampling was applied, and consent was obtained before data collection. A structured questionnaire was used as the study tool, and the collected data was analysed in SPSS 20.

Results:

A total of 98 personnel responded, among which 67.3% were males and 32.7% were females, with a median age of 36 (32–42) years. Only 6.1% of the workers had received training on ergonomics. The prevalence of work-related musculoskeletal disorders was 82.7%, and more than two-thirds of the participant’s life outside of work was affected by this. More than two-thirds (69.4%) felt their work environment was not safe, and surgeons performing open surgery were at lower odds of feeling that their work environment was safe.

Conclusion:

There is a high prevalence of work-related musculoskeletal disorders among healthcare providers working inside the operating room, and the majority had their body position deviated from neutral most of the time during the surgery. There is a deficiency in ergonomic practices, which demands an effective intervention.
Comparative analysis of automated breast volume scanner (ABVS) combined with conventional hand-held ultrasound and mammography in female breast cancer detection
Authors: Sherchan Amir , Liang Jin Tian , Sherchan Bhakti , Suwal Sundar , Katwal Shailendra
Published: December 2023

Objective and background:

This study aimed to compare the diagnostic value of an automated breast volume scanner (ABVS) combined with conventional hand-held ultrasound and mammography in detecting female breast cancer. Early detection is vital in improving patient outcomes for this prevalent disease.

Methods:

Seventy-eight suspicious breast lesions from 60 patients were examined between August 2019 and July 2020. Each patient underwent ABVS, conventional hand-held ultrasound, and mammography. Diagnostic values, including coincidence rate, sensitivity, specificity, positive predictive value, and negative predictive value, were calculated using histopathology results as the “gold standard.”

Results:

Histopathology confirmed 55 malignant (70.51%) and 23 benign lesions (29.48%). ABVS combined with conventional hand-held ultrasound identified 56 malignant (52 confirmed, 4 benign) and 22 benign nodules (3 confirmed, 19 benign). Mammography detected 48 malignant (45 confirmed, 3 benign) and 30 benign nodules (10 confirmed, 20 benign). ABVS combined with conventional hand-held ultrasound had a sensitivity of 94.5%, specificity of 82.6%, positive predictive value of 92.9%, and negative predictive value of 86.4%. Mammography showed a sensitivity of 81.8%, specificity of 87.0%, positive predictive value of 93.8%, and negative predictive value of 66.7%.

Conclusion:

ABVS combined with conventional hand-held ultrasound showed high diagnostic value in detecting female breast cancer. The “convergence sign” in the coronal section played a significant role. It slightly outperformed mammography and offered advantages in terms of cost, convenience, comfort, and absence of radiation. Further promotion and implementation are supported.
Risk stratification, prevention and management of perioperative corneal abrasion for non-ocular surgery: Systematic Review
Authors: Liyew Temesgen Misganaw , Mersha Abraham Tarekegn , Admassie Belete Muluadam , Arefayne Nurhusen Riskey
Published: December 2023

Background:

A corneal abrasion is a flaw in the cornea’s epithelial surface, which is located in the front of the eye. It causes recurrent erosions, corneal inflammation, and chronic corneal defects. In a context with limited resources, the goal of this review was to provide an evidence-based procedure for perioperative risk stratification, prevention, and management of corneal abrasion during non-ocular surgery.

Methods:

A medical search engines of PUBMED, GOOGLE SCHOLAR, COCHRANE REVIEW, and PUBMED CENTERAL to get access for current and updated evidence on procedures on risk stratification, prevention and management of corneal abrasion for non-ocular surgery. The authors formulate the key questions, scope, and articles written in English language, human study focuses on corneal abrasion, articles in the last 20 year was implemented to identify or filter high-level evidences were included. Reports contain corneal abrasion due to ocular surgery were excluded. All the research articles, which were identified from searches of electronic databases, were imported into Endnote software, duplicate were removed advanced search strategy of electronic sources from databases and websites was conducted using Boolean operators (cornea AND (abrasion OR injury OR laceration)) AND (“Perioperative Period” OR “general anesthesia”). Screening of literatures was conducted with proper appraisal checklist. This review was reported in accordance with preferred reporting items for systematic reviews and meta-analyses (PRISMA) 2020 statement.

Results:

From 8767 identified articles, two hundred articles were removed for duplication and 7720 studies were excluded, 1205 articles were retrieved and evaluated for eligibility. Finally, 24 were included in this systematic review. Advanced age, Prominent eyes, , exophthalmus, ocular surface abnormalities (dry eye), expected duration of surgery (>1 h), the favourable position of the surgery, prone,Trendelenburg and lateral, risk of bleeding, surgical site of the surgery(head /neck) and diabetes mellitus were risk for corneal abrasion. The use of appropriate intervention with pharmacological and Non-pharmacological strategies minimizes the occurrence of perioperative corneal abrasion was crucial for the quality of care.

Conclusion:

Preventing and managing corneal abrasion improves patients’ quality of life. However, there was insufficient evidence to draw conclusions, and high-quality trials of multimodal interventions matched to risk stratification and prevention of corneal abrasion needed to provide robust evidence to guide prevention and management of perioperative corneal abrasion.
Help-seeking behaviour towards anxiety among undergraduate students of Nepal: a web-based cross-sectional study
Authors: Aryal Richa , Rajbanshi Manish , Pokhrel Sushma , Regmi Sushama , Mali Prajita , Baskota Swechhya
Published: December 2023

Background:

Stigma among mental disorders like anxiety has been identified as an important barrier in help-seeking by national policymakers. Anxiety disorders are quite common among college students, and their severity and prevalence are growing. This study aimed to assess help-seeking behavior (HSB) towards anxiety among undergraduate students of Kathmandu University (KU).

Methodology:

A web-based cross-sectional study was conducted among 422 undergraduate students. General Help-Seeking Questionnaire (GHSQ) tool was used to assess HSB. Frequencies, percentages, mean, and Standard Deviation were calculated to assess the characteristics of the participants. Factors associated with HSB were examined using Chi-Square test. Pearson correlation was determined to find out the association between professional and informal sources for seeking help. All the tests were carried out at the statistically significant level at a P-value of 0.05.

Results:

The mean (±SD) age was 20.3±1.1 years in this study. This study demonstrated that 36.5 and 17.5% of the participants were extremely likely to seek help from parents and psychiatrists towards anxiety, respectively. Sex (OR=1.5, 95% CI: 1.0–1.3) was significantly associated with parents, education was significantly associated with parents (OR=0.4, 95% CI: 0.2–0.6), and friends (OR=0.5, 95% CI: 0.3–0.9), meanwhile, ethnicity (OR=0.6, 95% CI: 0.4–0.9), and residence (OR=0.5, 95% CI: 0.3–0.8) were significantly associated with psychiatrists and psychologists for help-seeking behavior, respectively. Fear of criticism (34.1%) and stigma (20.3%) were the main reasons for not seeking help among the participants. The maximum number of participants (41.5%) preferred to seek help immediately if they ever experienced anxiety. This study showed professional and informal sources were positively correlated with anxiety (rpi=0.3) at a P-value <0.05.

Conclusion:

This study showed that students preferred to seek help from informal sources rather than professional sources. In addition, there is still stigma and fear among students regarding mental health. This study suggests that there is a need to have psychosocial intervention at colleges and educational institutions in order to promote professional help-seeking for any mental disorders including anxiety.
Role of MMP-9, TIMP-1 as markers of lung imaging and functional abnormality of COVID-19
Authors: Rosyid Alfian Nur , Puspitasari Arina Dery , Sensusiati Anggraini Dwi , Soebakti Erika , Puspitasari Yessy , Robiul Fuadi Muhammad , Nugraha Jusak , Amin Muhammad
Published: December 2023

Background:

Pneumonia is common in COVID-19 patients, characterized by abnormal lung imaging and oxygen demand. Lung inflammation may affect the extracellular matrix balance in correlation with lung abnormalities and their severity and clinical implications.

Objective:

to analyze the level of MMP-9 and TIMP-1 as biomarkers of lung abnormalities, severity, and mortality of COVID-19.

Methods:

Adult COVID-19 patients hospitalized between March and November 2021 were included in the study. Patients with HIV, pregnancy, and chronic respiratory disease were excluded from the study. Complete Blood count, MMP-9, TIMP-1, and Blood gas analysis measured from the blood during admission. Chest X-ray was categorized using the Brixia score.

Results:

The increase of MMP-9 level in severe was higher than in non-severe (P<0.05). The decrease of TIMP-1 level in non-severe was lower than in severe (P<0.05). The increase in MMP-9 correlated to TIMP-1 with a linear R2=0.945. MMP-9 was related significantly to severity (r=0.242) and oxygen demand (FiO2) (r=0.263). Severity was also related to comorbidity (r=0.313), Brixia score (r=0.650), and mortality (r=0.458). MMP-9 and TIMP-1 correlated inversely significant with PaO2/FiO2 (r=−0.291 and r=−0.283) and the Brixia score (r=0.247 and r=0.254). Brixia score correlated with oxygen marker. Mortality related to severity (r=0.458), Brixia score (r=0.405), and oxygen demand (FiO2) (r=0.471), but not related to MMP-9 or TIMP-1.

Conclusion:

MMP-9 may contribute to COVID-19 severity. MMP-9 and TIMP-1 were related to lung abnormalities but not related to mortality. This study may present the potential benefit of MMP-9 inhibitor therapy and TIMP-1 exogen administration.
Unraveling a rare splenic pathology: a case report of a benign hemorrhagic spleen with primary congenital splenic epidermoid cysts
Authors: Al Laham Omar , Sharaf Aldeen Rahaf , Al Kurdi M Fadi , Alshiekh Ali , Bozo Maher
Published: December 2023

Introduction and importance:

A primary congenital splenic epidermoid cyst is an immensely rare pathology with mostly unknown epidemiological parameters. Misdiagnosis can easily happen and this results in life-threatening ramifications for patients. Considering this pathology as a potential differential diagnosis allows for the required surgical intervention to be timely accomplished. In this case, the authors are documenting this pathology and presenting how it was successfully managed via proper and informed preoperative analysis and meticulous intraoperative technique.

Case presentation:

Hereby, we portray the exceptionally rare case of a 7-year-old male who presented to our surgical clinic complaining of a sudden left hypochondriac pain with early satiety for 1 month’s duration. The preoperative radiological assessment displayed numerous splenic cystic lesions throughout the splenic parenchyma.

Clinical discussion:

Resection of the cysts was accomplished via total splenectomy. The ensuing histopathological analysis via Hematoxylin and Eosin of the resected specimens established the diagnosis of a congested hemorrhagic spleen with multiple primary congenital splenic epidermoid cysts.

Conclusion:

Primary congenital splenic epidermoid cysts are an extremely rare type of splenic pathology. There is profound scarcity amidst the published literature regarding it. This merits in-depth study and apt documentation to raise awareness regarding this pathology as a potential differential diagnosis in cases of abdominal pain. Documentation allows us to set up proper and innovative clinical and surgical protocols for these patients. Based on our conclusive review of the published literature, the authors conclude that ours is the first ever documented case from our country of a primary congenital splenic epidermoid cyst.
The Clinical Characteristics of Heart Rate Variability After Stroke
Authors: Bai Xue , Wang Na , Si Yueqiao , Liu Yunchang , Yin Ping , Xu Chunmei
Published: December 2023

The autonomic nervous system dysfunction has been reported in up to 76% of stroke patients 7 days after an acute stroke. Heart rate variability (HRV) is one of the important indicators reflecting the balance of sympathetic and parasympathetic nerves. Therefore, we performed a systematic literature review of existing literature on the association between heart rate variability and the different types of stroke. We included studies published in the last 32 years (1990 to 2022). The electronic databases MEDLINE and PubMed were searched. We selected the research that met the inclusion or exclusion criteria. A narrative synthesis was performed. This review aimed to summarize evidence regarding the potential mechanism of heart rate variability among patients after stroke. In addition, the association of clinical characteristics of heart rate variability and stroke has been depicted. The review further discussed the relationship between post-stroke infection and heart rate variability, which could assist in curbing clinical infection in patients with stroke. HRVas a noninvasive clinical monitoring tool can quantitatively assess the changes in autonomic nervous system activity and further predict the outcome of stroke. HRV could play an important role in guiding the clinical practice for autonomic nervous system disorder after stroke.
HyGAnno: Hybrid graph neural network-based cell type annotation for single-cell ATAC sequencing data
Authors: Zhang Weihang , Cui Yang , Loza Martin , Park Sung-Joon , Nakai Kenta
Published: December 2023

Reliable cell type annotations are crucial for investigating cellular heterogeneity in single-cell omics data. Although various computational approaches have been proposed for single-cell RNA sequencing (scRNA-seq) annotation, high-quality cell labels are still lacking in single-cell ATAC sequencing (scATAC-seq) data, because of extreme sparsity and inconsistent chromatin accessibility between datasets. This calls for novel cell type annotation methods in scATAC-seq, to better explore cell type-specific gene regulatory mechanisms and provide a complementary epigenomic layer to scRNA-seq data. Here, we present a novel automated cell annotation method that transfers cell type information from a well-labeled scRNA-seq reference to an unlabeled scATAC-seq target, via a parallel graph neural network, in a semi-supervised manner. Unlike existing methods that utilize only gene expression or gene activity features, HyGAnno integrates genomewide accessibility peak features to facilitate the training process. In addition, HyGAnno reconstructs a reference-target cell graph that can be used to detect cells with low prediction reliability, according to their specific graph connectivity patterns. HyGAnno was tested using large datasets and demonstrated the advantages of accurate cell annotation, interpretable cell embedding, robustness to noisy reference data, and adaptability to tumor tissues.
The balance between ATR and DDK activities controls TopBP1-mediated locking of dormant origins at the pre-IC stage
Authors: Koundrioukoff Stéphane , Kim Su-Jung , Alary Nathan , Toffano Antoine , Melendez-Garcia Rodrigo , Wu Xia , Liu Yaqun , Gnan Stefano , El-Hilali Sami , Brison Olivier , Rosselli Filippo , Chen Chun-Long , Debatisse Michelle
Published: December 2023

Replication stress, a major hallmark of cancers, and ensuing genome instability source from impaired progression of replication forks. The first line of defense against fork slowing is compensation, a long-described process that elicits firing of otherwise dormant origins. It remains unclear whether compensation requires activation of the DNA replication checkpoint or passively results from lengthening of the window of time during which dormant origins can fire when fork progression slows, or both. Using molecular DNA combing we show here that a linear relationship ties inter-origin distances to fork speeds, independently of the checkpoint status. We called this line “stressline” and further show that its slope enables precise quantification of the compensation efficiency. Comparison of the slopes in different genetic backgrounds reveals that compensation requires ATR, not CHK1, while TopBP1 and CDC7/DBF4 repress dormant origin activation. These results strongly suggest that TopBP1 locks dormant origins at the pre-IC stage and that ATR and DDK oppose to control the conversion of dormant pre-ICs into functional salvage origins. Both passive and active processes thus contribute to compensation. Moreover, Repli-seq and OK-seq analyses confirm the activating role of ATR and permit development of ATRAP-seq, a new procedure allowing mapping of early constitutive origins.
Wind Gates Olfaction Driven Search States in Free Flight
Authors: Stupski S. David , van Breugel Floris
Published: December 2023

For organisms tracking a chemical cue to its source, the motion of their surrounding fluid provides crucial information for success. Swimming and flying animals engaged in olfaction driven search often start by turning into the direction of an oncoming wind or water current. However, it is unclear how organisms adjust their strategies when directional cues are absent or unreliable, as is often the case in nature. Here, we use the genetic toolkit ofDrosophila melanogasterto develop an optogenetic paradigm to deliver temporally precise “virtual” olfactory experiences for free-flying animals in either laminar wind or still air. We first confirm that in laminar wind flies turn upwind. Furthermore, we show that they achieve this using a rapid (∼100 ms) turn, implying that flies estimate the ambient wind direction prior to “surging” upwind. In still air, flies adopt remarkably stereotyped “sink and circle” search state characterized by ∼60°turns at 3-4 Hz, biased in a consistent direction. Together, our results show thatDrosophila melanogasterassess the presence and direction of ambient wind prior to deploying a distinct search strategy. In both laminar wind and still air, immediately after odor onset, flies decelerate and often perform a rapid turn. Both maneuvers are consistent with predictions from recent control theoretic analyses for how insects may estimate properties of wind while in flight. We suggest that flies may use their deceleration and “anemometric” turn as active sensing maneuvers to rapidly gauge properties of their wind environment before initiating a proximal or upwind search routine.
Setting a trajectory for CO2emission reduction in academic research: a case study of a French biophysics laboratory
Authors: Giuglaris Caroline , de Seze Jean
Published: December 2023

Climate change is a scientifically proven phenomenon caused by anthropic activities, which requires urgent and significant reductions in greenhouse gas emissions. Despite the increasing vocalization of scientists advocating for political action, the issue of the environmental impact of academic research has been neglected for some time. Now, field-dependent initiatives have emerged, such as the non-profit organization My Green Lab, which delivers green certifications to biology and chemistry labs, and institute-dependent programs, such as the Max Planck Sustainability Network. In France, an independent collective was founded in 2019 to address the environmental footprint of academic research following the COP 15 Paris Agreement: Labos 1Point5. Building on their resources and methodology, we have quantified the overall carbon footprint of our biophysics laboratory, considering energy consumption, purchases and travel, for the year 2021. We investigate how this footprint would decrease by 2030 following systemic changes (change in the energy mix, improvements from suppliers), and we propose scenarios based on additional voluntary initiatives to reach a final reduction of -50% compared to the 2021 baseline, following IPCC targets. We have now formed a group of more than 20 colleagues to achieve this goal, emphasizing the importance of collective action. Finally, we provide advice based on our own experience to assist others in addressing the environmental impact of academic research in their respective laboratories.
A benchmarked comparison of software packages for time-lapse image processing of monolayer bacterial population dynamics
Authors: Ahmadi Atiyeh , Courtney Matthew , Ren Carolyn , Ingalls Brian
Published: December 2023

Time-lapse microscopy offers a powerful approach for analysing cellular activity. In particular, this technique is valuable for assessing the behaviour of bacterial populations, which can exhibit growth and intercellular interactions in monolayer. Such time-lapse imaging typically generates large quantities of data, limiting the options for manual investigation. Several of image processing software packages have been developed to facilitate analysis. It can thus be a challenge to identify the software package best suited to a particular research goal. Here, we compare four software packages that support analysis of 2D time-lapse images of cellular populations: CellProfiler, SuperSegger-Omnipose, DeLTA, and FAST. We compare their performance against benchmarked results on time-lapse observations ofE. colipopulations. Performance varies across the packages, with each of the four out-performing the others in at least one aspect of the analysis. Not surprisingly, the packages that have been in development for longer showed the strongest performance. We found that deep-learning based approaches to object segmentation outperformed traditional approaches, but the opposite was true for frame-to-frame object tracking. We offer these comparisons, together with insight on usability, computational efficiency, and feature availability, as a guide to researchers seeking image processing solutions.

Significance Statement

Time-lapse microscopy provides a detailed window into the world of bacterial behavior. However, the vast amount of data produced by these techniques is difficult to analyze manually. We have analysed four software tools designed to process such data and compared their performance, using populations of commonly studied bacterial species as our test subjects. Our findings offer a roadmap to scientists, helping them choose the right tool for their research. This comparison bridges a gap between microbiology and computational analysis, streamlining research efforts.
Single-cell profiling reveals the impact of genetic alterations on the differentiation of inflammation-induced colon tumors
Authors: Ghobashi Ahmed H. , Lanzloth Rosie , Ladaika Christopher A. , O’Hagan Heather M.
Published: December 2023

Genetic mutations and chronic inflammation of the colon contribute to the development of colorectal cancer (CRC). Using a murine model of inflammation-induced colon tumorigenesis, we determined how genetic mutations alter colon tumor cell differentiation. Inflammation induced by enterotoxigenicBacteroides fragilis(ETBF) colonization of multiple intestinal neoplasia (MinApcΔ716/+) mice triggers loss of heterozygosity ofApccausing colon tumor formation. Here, we report that the addition ofBRAFV600Emutation (BRAFFV600ELgr5tm1(Cre/ERT2)CleMinApcΔ716/+, BLM) or knocking outMsh2(Msh2LoxP/LoxPVil1-creMinApcΔ716/+, MSH2KO) in the Min model altered colon tumor differentiation. Using single cell RNA-sequencing, we uncovered the differences between BLM, Min, and MSH2KO tumors at a single cell resolution. BLM tumors showed an increase in differentiated tumor epithelial cell lineages and a reduction in the stem cell population. In contrast, MSH2KO tumors were characterized by an increased stem cell population that had higher WNT signaling activity compared to Min tumors. Additionally, comparative analysis of single-cell transcriptomics revealed that BLM tumors had higher expression of transcription factors that drive differentiation, such asCdx2,than Min tumors. Using RNA velocity, we were able to identify additional potential regulators of BLM tumor differentiation such as NDRG1. The role of CDX2 and NDRG1 as putative regulators for BLM tumor cell differentiation was verified using organoids derived from BLM tumors. Our results demonstrate the critical connections between genetic mutations and cell differentiation in inflammation-induced colon tumorigenesis. Understanding such roles will deepen our understanding of inflammation-associated colon cancer.
Transcription factor activity profiling reveals the role of REST and LEF1 in the recovery from depression
Authors: Yamamoto Hajime , Araki Satomi , Onodera Ryoma , Go Yasuhiro , Abe Kentaro
Published: December 2023

Psychophysiological disorders chronically impair brain functions, often accompanied by dysregulation of multiple genes, suggesting a multifaceted etiology behind the symptoms. To explore transcription factors (TFs) involved in such transcriptomic changes, we analyzed TF-activity profiles (TFAPs) from the brains of mice experienced chronic stress, and revealed alteration in TF-activity correlating with their pathophysiological phenotypes. We identified REST/NRSF and TCF/LEF associated with depressive phenotypes and discovered that neuropsychiatric drugs sertraline and lithium influence REST- and TCF/LEF-activity, both in vitro and in vivo, thereby affecting gene expression profiles. Pharmacological or genetic manipulation of REST- or TCF/LEF-activity in defeated mice impacts post-stress recovery from depressive phenotypes, with combined treatment further augmenting the outcomes. Our TFAP analysis enhances understanding of molecular mechanisms underpinning chronic diseases, aiding future therapeutic strategy development.
Multimodal generation of astrocyte by integrating single-cell multi-omics data via deep learning
Authors: Mao Jiashun , Wang Jianmin , Zeb Amir , No Kyoung Tai
Published: December 2023

Obtaining positive and negative samples to examining several multifaceted brain diseases in clinical trials face significant challenges. We propose an innovative approach known as Adaptive Conditional Graph Diffusion Convolution (ACGDC) model. This model is tailored for the fusion of single cell multi-omics data and the creation of novel samples. ACGDC customizes a new array of edge relationship categories to merge single cell sequencing data and pertinent meta-information gleaned from annotations. Afterward, it employs network node properties and neighborhood topological connections to reconstruct the relationship between edges and their properties among nodes. Ultimately, it generates novel single-cell samples via inverse sampling within the framework of conditional diffusion model. To evaluate the credibility of the single cell samples generated through the new sampling approach, we conducted a comprehensive assessment. This assessment included comparisons between the generated samples and real samples across several criteria, including sample distribution space, enrichment analyses (GO term, KEGG term), clustering, and cell subtype classification, thereby allowing us to rigorously validate the quality and reliability of the single-cell samples produced by our novel sample method. The outcomes of our study demonstrated the effectiveness of the proposed method in seamlessly integrating single-cell multi-omics data and generating innovative samples that closely mirrored both the spatial distribution and bioinformatic significance observed in real samples. Thus, we suggest that the generation of these reliable control samples by ACGDC holds substantial promise in advancing precision research on brain diseases. Additionally, it offers a valuable tool for classifying and identifying astrocyte subtypes.