bluuebunny/crossref_metadata_2025_split huggingface dataset:
SRRM4-mediated REST to REST4 dysregulation promotes tumor growth and neural adaptation in breast cancer leading to brain metastasis
Authors: Deshpande Krutika , Martirosian Vahan , Nakamura Brooke N , Das Diganta , Iyer Mukund , Reed Max , Shao Ling , Bamshad Daniella , Buckley Noel J , Neman Josh 
Published: September 2023

Abstract

Background
Effective control of brain metastasis remains an urgent clinical need due a limited understanding of the mechanisms driving it. Although the gain of neuro-adaptive attributes in breast-to-brain metastases (BBMs) has been described, the mechanisms that govern this neural acclimation and the resulting brain metastasis competency are poorly understood. Herein, we define the role of neural-specific splicing factor Serine/Arginine Repetitive Matrix Protein 4 (SRRM4) in regulating microenvironmental adaptation and brain metastasis colonization in breast cancer cells.

Methods
Utilizing pure neuronal cultures and brain-naive and patient-derived BM tumor cells, along with in vivo tumor modeling, we surveyed the early induction of mediators of neural acclimation in tumor cells.

Results
When SRRM4 is overexpressed in systemic breast cancer cells, there is enhanced BBM leading to poorer overall survival in vivo. Concomitantly, SRRM4 knockdown expression does not provide any advantage in central nervous system metastasis. In addition, reducing SRRM4 expression in breast cancer cells slows down proliferation and increases resistance to chemotherapy. Conversely, when SRRM4/REST4 levels are elevated, tumor cell growth is maintained even in nutrient-deprived conditions. In neuronal coculture, decreasing SRRM4 expression in breast cancer cells impairs their ability to adapt to the brain microenvironment, while increasing SRRM4/RE-1 Silencing Transcription Factor (REST4) levels leads to greater expression of neurotransmitter and synaptic signaling mediators and a significant colonization advantage.

Conclusions
Collectively, our findings identify SRRM4 as a regulator of brain metastasis colonization, and a potential therapeutic target in breast cancer.
How variable progenitor clones construct a largely invariant neocortex
Authors: Shen Zhongfu , Yang Jiajun , Zhang Qiangqiang , Wang Kuiyu , Lv Xiaohui , Hu Xiaolin , Ma Jian , Shi Song-Hai 
Published: September 2023

ABSTRACT
The neocortex contains a vast collection of diverse neurons organized into distinct layers. While nearly all neocortical neurons are generated by radial glial progenitors (RGPs), it remains largely unclear how a complex yet organized neocortex is constructed reliably and robustly. Here, we show that the division behavior and neuronal output of RGPs are highly constrained with patterned variabilities to support the reliable and robust construction of the mouse neocortex. The neurogenic process of RGPs can be well-approximated by a consistent Poisson-like process unfolding over time, producing deep to superficial layer neurons progressively. The exact neuronal outputs regarding layer occupation are variable; yet, this variability is constrained systematically to support all layer formation, largely reflecting the variable intermediate progenitor generation and RGP neurogenic entry and exit timing differences. Together, these results define the fundamental features of neocortical neurogenesis with a balanced reliability and variability for the construction of the complex neocortex.
Neurogenesis in primates versus rodents and the value of non-human primate models
Authors: Zhang Runrui , Quan Hongxin , Wang Yinfeng , Luo Fucheng 
Published: September 2023

ABSTRACT
Neurogenesis, the process of generating neurons from neural stem cells, occurs during both embryonic and adult stages, with each stage possessing distinct characteristics. Dysfunction in either stage can disrupt normal neural development, impair cognitive functions, and lead to various neurological disorders. Recent technological advancements in single-cell multiomics and gene-editing have facilitated investigations into primate neurogenesis. Here, we provide a comprehensive overview of neurogenesis across rodents, non-human primates, and humans, covering embryonic development to adulthood and focusing on the conservation and diversity among species. While non-human primates, especially monkeys, serve as valuable models with closer neural resemblance to humans, we highlight the potential impacts and limitations of non-human primate models on both physiological and pathological neurogenesis research.
ORCHID: A phase II study of Olaparib in Metastatic Renal Cell Carcinoma Patients HarborIng a BAP1 or Other DNA Repair Gene Mutations
Authors: Ged Georges , Rifkind Irina , Tony Lori , Daugherty Keegan , Michalik Amber , Wang Hao , Carducci Michael , Markowski Mark 
Published: September 2023

Abstract

Background
DNA damage repair genes alterations (DDRa) are frequent events in renal cell carcinoma (RCC), including BAP1 and other DDRa. Olaparib is a poly ADP ribose polymerase inhibitor (PARPi) that is FDA-approved for the treatment of several malignancies with DDRa. Preclinical models demonstrated synthetic lethality with PARPi in RCC cell lines including BAP1 mutant lines. Here we report an interim analysis of the ORCHID study investigating the clinical activity of single agent olaparib in patients (pts) with advanced RCC (aRCC) harboring BAP1 other select DDRa.

Methods
We conducted a single center, single arm, investigator-initiated Phase 2 trial of olaparib in pts with aRCC. Eligible pts harbored select DDRa and had prior therapy with immune checkpoint inhibitors (ICIs) and/or VEGF-TKI. Pts were treated with olaparib at an initial dose of 150mg twice which was increased to 300mg twice daily after one month if well tolerated. The primary endpoint is disease control rate (DCR) by RECIST v1.1 (including complete response (CR), partial response (PR), and stable disease (SD) &gt;6 months). Secondary endpoints included objective response rate (ORR), progression free survival (PFS), and safety.

Results
Eleven pts were enrolled with a median age of 59 years (48-72) including 9 pts with clear cell RCC and 2 pts with unclassified RCC. Most pts had BAP1 mutations (Table). 36% of pts had history of brain metastasis. Median number of prior lines of therapies was 2 (1-6) and all pts received prior ICI. The study met the pre-specified Simon’s 2 stage design for the first stage with 22% DCR in the evaluable pts (2/9), including deep PR (&gt;70% reduction in tumor volume) and SD of 10 months. Both pts harbored BAP1 mutations. An additional pt with BRCA1 mutation had 20% decrease in measurable disease. There were no treatment related adverse events resulting in study discontinuation.

Conclusions
This is the first study investigating single agent PARPi in RCC with the interim trial analysis indicating promising activity of olaparib in aRCC pts with BAP1 mutations including one pt with deep PR. These results support further development of PARPi in this setting.
Public Support for Democracy in the United States Has Declined Generationally
Authors: Claassen Christopher , Magalhães Pedro C 
Published: September 2023

Abstract
Support for democracy in the United States, once thought to be solid, has now been shown to be somewhat shaky. One of the most concerning aspects of this declining attachment to democracy is a marked age gap, with younger Americans less supportive of democracy than their older compatriots. Using age-period-cohort analysis of 12 national surveys collected between 1995 and 2019, we show that this age gap is largely a function of a long-term generational decline in support for democracy, with little evidence of an independent life-cycle effect apparent. The combination of generational decline without a positive and counterbalancing life-cycle effect offers a sober prognosis of how support for democracy in the United States might look in the future.
Assessment of natural radioactivity, radon gas and soil characteristics along the Volta Lake in the Kpando municipality of Volta region, Ghana
Authors: Amable Anthony Selorm Kwesi , Otoo Francis , Buah-Bassuah Paul Kingsley , Twum Anthony Kwabena 
Published: September 2023

Abstract
Assessment of radionuclides, indoor radon (222RnI), radon exhalation (222Rnex), and soil characteristics in the coastal part of Kpando has been studied using HPGe, CR-39 and sieving techniques. Statistical analysis between radionuclides, radon levels and soil characteristics was done using Pearson’s correlation. The mean radionuclide concentration, radon levels and soil characteristics were obtained as 226Ra (23.1 ± 1.4 Bq per kg), 232Th (34.6 ± 2.9 Bq per kg), 40K (187.1 ± 13.7 Bq per kg), 222RnI (64.70 ± 2.7 Bq per m3), 222Rnex (7.9 ± 0.5 μBq per m2h), sandy (45.9 ± 3.9%), silt (40.7 ± 3.1%), clay (13.5 ± 0.8%), porosity (0.6 ± 0.1) and moisture (7.6 ± 0.8%). Radiological effects estimated were within recommended limits. The maximum positive and negative coefficients exist between 222Ra/222Rnex (1.0) and 222Rnex/MC (−0.9), respectively. Radon exhalation correlates better with soil characteristics. The statistical analysis indicated that soil characteristics have significant effects on radionuclides and radon levels in soils and dwellings.
Preclinical Evidence for the Use of Oral Mesenchymal Stem Cell-Derived Extracellular Vesicles in Bone Regenerative Therapy: A Systematic Review
Authors: Olaechea Allinson , Benabdellah Karim , Vergara-Buenaventura Andrea , Gómez-Melero Sara , Cafferata Emilio A , Meza-Mauricio Jonathan , Padial-Molina Miguel , Galindo-Moreno Pablo 
Published: September 2023

Abstract
The development of extracellular vesicles (EVs) therapies has revolutionized personalized medicine, opening up new possibilities for treatment. EVs have emerged as a promising therapeutic tool within this field due to their crucial role in intercellular communication across various cell types and organisms. This systematic review aims to evaluate the therapeutic potential of oral mesenchymal stem cell (MSC)-derived EVs for bone regeneration, specifically focusing on findings from preclinical models. Sixteen articles meeting the inclusion criteria were selected following document analysis. The biological effects of oral MSC-derived EVs predominantly involve the upregulation of proteins associated with angiogenesis, and inflammation resolution, alongside the downregulation of proinflammatory cytokines. Moreover, these therapeutic agents have been found to contain a significant quantity of different molecules (proteins, lipids, DNA, microRNAs, etc) further contributing to their modulatory potential. The findings from this systematic review underscore that oral MSC-derived EVs, irrespective of their specific population, have the ability to enhance the osteogenic repair response in maxillary bone or periodontal defects. In summary, this systematic review highlights the promising potential of oral MSC-derived EVs for bone regeneration based on evidence from preclinical models. The comprehensive assessment of their biological effects and the presence of microRNAs underscores their therapeutic significance. These findings support the utilization of oral MSC-derived EVs in enhancing the osteogenic repair response in various maxillary bone or periodontal defects, providing insights into the mechanisms involved and potential therapeutic applications in the field of personalized medicine.
Developing a culturally tailored digital health intervention for insomnia in Black women
Authors: Zhou Eric S , Revette Anna , Ritterband Lee M , Bethea Traci N , Delp Lauren , Simmons Patricia D , Rosenberg Lynn 
Published: September 2023

Abstract
Insomnia disorder is highly prevalent among Black women. Cognitive-behavioral therapy for insomnia (CBT-I) is considered the optimal treatment, but very little efficacy research has been conducted in minority populations. Culturally tailoring intervention content may increase participant engagement and improve treatment outcomes. We culturally tailored an Internet-delivered CBT-I program (Sleep Healthy Using the Internet; SHUTi) for Black women. First, relevant stakeholders were identified. Semi-structured interviews were conducted after stakeholders completed each of the six SHUTi intervention sessions. Questions focused on improving program relatability and engagement for Black women. Key themes pertinent to peripheral, evidential, and sociocultural strategies for cultural adaptation were identified using thematic content analysis, and adaptation recommendations were developed. A total of 50 interviews, across 9 stakeholders, were conducted. Two overarching themes were identified: (i) there was limited visual African American representation, and (ii) there was a lack of diversity in the environments and lifestyles of the patient vignettes. Respondents provided peripheral, evidential, and sociocultural recommendations for program modifications, emphasizing the importance of race-concordant visual content and didactic content exploring the diverse cultural and social contexts in which insomnia occurs for Black women. As more diverse patients seek evidence-based insomnia treatment, digital health interventions must consider whether it is therapeutically important to address and tailor for cultural differences. Here, stakeholders made clear recommendations for taking cultural contexts into account to improve patient engagement with the program. Further research should work to understand the extent to which culturally tailored interventions are beneficial for health outcomes among minority populations.
Taxonomic inflation and a reconsideration of speciation in the Andes: the case of the high-elevation tree frogDendropsophus molitor(Anura: Hylidae)
Authors: Arias-Cárdenas Alexandra , Barrientos Lucas S , Pardo-Diaz Carolina , Paz Andrea , Crawford Andrew J , Salazar Camilo 
Published: September 2023

AbstractDendropsophus molitor is a hylid frog endemic to the Eastern Cordillera of the Colombian Andes, where it exhibits extensive geographic variation in size and colour pattern. Previous multivariate analyses of acoustic and genetic data suggested that northern and southern populations of D. molitor were distinct lineages, and consequently, the northern populations were described as Dendropsophus luddeckei. In this study, we conducted morphometric and genetic analyses of populations of D. molitor and D. luddeckei to test the validity of this recent taxonomic split. We sequenced the mitochondrial genes 12S, 16S, and COI, and the nuclear marker POMC, and also tested whether variation in the MC1R gene was associated with colour polymorphism in these frogs. Phylogenetic analyses recovered D. molitor and D. luddeckei as polyphyletic and species delimitation tests failed to recover them as separate lineages. Genetic differentiation between populations was mostly explained by high intra- and interpopulation variation in the absence of a north-south split, and we found no differences in morphometry between northern and southern populations. In addition, the coding region of MC1R is not associated with colour polymorphism. Thus, multiple lines of evidence suggest that D. luddeckei is not a valid species and D. molitor should be considered a single species. Our study highlights the danger of taxonomic inflation in the face of limited geographic sampling and a lack of clear diagnostic characters.
Prevalence of trichomoniasis infection among adults in Nigerian community settings
Authors: Obetta K. Chukwuemeka , Ogbonna Innocent Okonkwo , Oyigbo Dorida Nneka , Ugwu Oliver Onyemaechi , Ugwu Kenneth Okonkwo , Onah Beatrice N. , Ugwunnadi Chinasa Maryrose , Acha Joseph O. , Chuke Ngozi Uzoamaka , Nkemjika Ogechi , Okoye Onyinyechi Elizabeth 
Published: September 2023

Background:

Trichomonas vaginalis (TV) is a sexually transmitted pathogen. The study was conducted to determine its prevalence among 300 adult patients in 4 public health facilities in the Nsukka District of Enugu State, Nigeria.

Method:
The researchers collected high vagina swabs and urine samples were collected from 150 men and 150 women, respectively. The specimens were scrutinized for color, odor of discharge and urine, and motile trichomoniasis.

Results:
The prevalence of the TV was 45.0% (135/300) with women showing the highest prevalence (63.7%). Among the patients attending the University of Nigeria, Nsukka Medical Center, the prevalence was the highest at 31.9%. TV infection was more common among older adults aged 38 to 47 years (39.3%), married adults (76.3%), and those with secondary education (68.9%). Urogenital analysis reported that males with pains during urination were 51.0% and males with penile tingling were 12.2%. The highest vaginal Hydrogen ion concentration level of 6.8 was observed in women aged 38 to 47 years. Additionally, the results reported that Vaginal candidiasis, Bacterial vaginosis, and Herpes simplex virus type 2 antibodies were not independently associated with TV infection. In the unadjusted analysis, the odds of TV infection were higher in men (8.1), while Chlamydia trachomatis infection was higher in women (8.8). Among the adults diagnosed with herpes simplex virus type 2 antibodies, the odds of TV infection were 3.9 for both men and women. Men with penile human papillomavirus infection had lower odds of TV infection (1.9), while women with vaginal human papillomavirus infection had higher odds of TV infection (2.2).

Conclusion:
The prevalence of TV infection is high among sexually active adults in the Nigerian community. It is therefore crucial to implement the increased public health actions such as regular and early diagnosis to reduce its prevalence.
Venoarterial extracorporeal membrane oxygenation for group B streptococcal toxic shock syndrome: A case report and literature review
Authors: Iwasaki Naoya , Sekino Motohiro , Tominaga Tetsuro , Tanaka Takeshi , Araki Hiroshi , Yano Rintaro , Matsumoto Sojiro , Ichinomiya Taiga , Higashijima Ushio , Nonaka Takashi , Izumikawa Koichi , Hara Tetsuya 
Published: September 2023

Rationale:
Streptococcal toxic shock syndrome (STSS) rapidly leads to refractory shock and multiple organ failure. The mortality rate among patients with STSS is 40%; however, most deaths occur within a few days of onset. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) may help avoid acute death in adult patients with STSS. However, the effectiveness of VA-ECMO is unclear. In this study, we report a case of group B STSS, which was successfully treated with VA-ECMO despite cardiopulmonary arrest (CPA) owing to rapidly progressive refractory shock.

Patient concerns:
A 60-year-old woman was hospitalized because of diarrhea and electrolyte abnormalities owing to chemoradiation therapy for rectal cancer. A sudden deterioration of her condition led to CPA. Conventional cardiopulmonary resuscitation was immediately performed but was ineffective. Therefore, VA-ECMO was initiated. Contrast-enhanced computed tomography revealed duodenal perforation. Hence, septic shock owing to peritonitis was diagnosed, and emergency surgery was performed under VA-ECMO. However, the patient had progressive multiple organ failure and required organ support therapy in the intensive care unit (ICU).

Diagnoses:
On day 2 in the ICU, blood and ascites fluid culture tests revealed beta-hemolytic streptococci, and the patient was finally diagnosed as having STSS caused by Streptococcus agalactiae.

Interventions:
Clindamycin was added to meropenem, vancomycin, and micafungin, which had been administered since the sudden deterioration. In addition, VA-ECMO, mechanical ventilation, blood purification therapy, and treatment for disseminated intravascular coagulation were continued.

Outcomes:
Thereafter, hemodynamics improved rapidly, and the patient was weaned off VA-ECMO on day 5 of ICU admission. She was transferred to a general ward on day 22 in the ICU.

Lessons:
In patients with fatal STSS and rapid progressive refractory shock or CPA, VA-ECMO may help to avoid acute death and improve prognosis by ameliorating tissue oxygenation and providing extra time to treat invasive streptococcal infection.
Clinical effect analysis of using medical glue versus conventional suturing to treat dog bite in children’s maxillofacial region after negative pressure sealing drainage: A randomized trial
Authors: Lisong Huang , Lianfu Wang , Jinhong Yang , Haibin Zhang 
Published: September 2023

Background:
To compare the clinical effectiveness of applying medical glue versus conventional suturing after primary suturing and continuous vacuum sealing drainage (VSD) technology in the treatment of facial wounds caused by dog bites in children’s maxillofacial region, with respect to operation time, wound infection rate, treatment effect, and patient satisfaction.

Methods:
From May 2020 to July 2022, 68 children with a dog bite in the maxillofacial region were randomly divided into medical glue and conventional suturing groups. The patients in both groups were treated with conventional debridement, tetanus and/or rabies immunization, and antibiotic therapy. The medical glue group was treated with VSD after the first-stage of the loose suture of the wound. After 5 days, the suture was removed, and the wound was tightly bonded with medical glue again. The conventional suturing group was treated with VSD after the first-stage of loose suture of the wound. The primary outcomes were the operation time and satisfaction of the 2 groups, and the secondary outcomes was the wound infection rate.

Results:
The operation time of the medical glue group was significantly lower than that of the conventional suturing group. However, there was no significant difference between the 2 groups in the wound infection rate. Still, the patient satisfaction was significantly better in the medical glue group than the conventional suturing group with statistically significant difference (P < .05).

Conclusion:
In conclusion, applying medical glue after using negative pressure sealing drainage in treating maxillofacial dog bites can reduce surgeons work intensity, lessen children’s pain, and improve the clinical treatment effect.
Herbal medicine for external use in acute gouty arthritis: A PRISMA-compliant systematic review and meta-analysis
Authors: Choi Su Hyeon , Song Ho-Sueb , Hwang Jihye 
Published: September 2023

Background:
Acute gouty arthritis is accompanied by severe pain during an acute attack. This systematic review aimed to evaluate the efficacy and safety of herbal medicines acting directly on the affected area of acute gouty arthritis for external use.

Methods:
An envelope search was performed using 4 electronic databases (CNKI, PubMed, EMBASE, Cochrane), resulting in 27 clinical studies from inception to February 2023. Randomized controlled trials on external use herbal medicines for acute gouty arthritis were considered. The assessed outcomes were total effective rate, uric acid level, pain score, and inflammatory factor levels such as erythrocyte sedimentation rate and C-reactive protein. Quality assessment and meta-analysis of the included randomized controlled trials were also performed.

Results:
Twenty-seven randomized controlled trials with a total of 1951 participants were included in the meta-analysis. All assessed outcomes including pain, inflammation, and uric acid levels, indicated that the treatment effects in the external use herbal medicine group were significantly better than those of the western medicine control group. Of the 10 studies mentioning side effects, no side effects were reported in 4, and in the remaining 6, the incidence of complications in the intervention group was much lower than that in the control group.

Conclusions:
This systematic review and meta-analysis suggests that external use herbal medicines may be a safe and effective alternative for treatment of pain and symptoms of acute gouty arthritis. However, owing to the heterogeneity of interventions, outcomes, and regional bias, further high-quality clinical trials on this topic are needed to confirm the level of evidence.