bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world efficacy and safety of cabozantinib following immune checkpoint inhibitor failure in Japanese patients with advanced renal cell carcinoma
Authors: Ishihara Hiroki , Nemoto Yuki , Tachibana Hidekazu , Fukuda Hironori , Yoshida Kazuhiko , Kobayashi Hirohito , Iizuka Junpei , Hashimoto Yasunobu , Kondo Tsunenori , Takagi Toshio 
Published: July 2023

Abstract

Background
Real-world data of cabozantinib after failure of immune checkpoint inhibitors for advanced renal cell carcinoma in Japanese population are limited. Additionally, prognostic factors of cabozantinib in this setting are still unknown.

Methods
We retrospectively evaluated data of 56 patients treated with cabozantinib subsequent to failed immune checkpoint inhibitors at four institutions. Regarding the efficacy profile, progression-free survival, overall survival and objective response rate were assessed. In terms of the safety profile, rate of adverse events, dose reduction and treatment interruption were assessed. Furthermore, risk factors of progression-free survival were analyzed.

Results
Twenty-nine patients (52%) were treated with cabozantinib as second-line therapy. Most frequent prior immune checkpoint inhibitor treatment was nivolumab plus ipilimumab combination therapy as first-line therapy (n = 30, 54%). Median progression-free survival and overall survival were 9.76 and 25.5 months, respectively, and objective response rate was 34%. All patients experienced at least one adverse event, and grade ≥ 3 adverse events were observed in 31 patients (55%). Forty-four (79%) and 31 (55%) patients needed dose reduction and treatment interruption, respectively. Multivariate analysis showed that reduced initial dose (i.e. &lt;60 mg) (hazard ratio: 2.50, P = 0.0355) and presence of lymph node metastasis (hazard ratio: 2.50, P = 0.0172) were independent factors of shorter progression-free survival.

Conclusion
Cabozantinib in Japanese patients with advanced renal cell carcinoma who failed immune checkpoint inhibitors was efficacious and had a manageable safety profile. These results appear to be similar to those of previous clinical trials.
Parasitization of the pedicle: a rare form of TRAM flap recurrence
Authors: Binks Matthew J , Guo CiCi , Sabanathan Danusha , Sathasivam Sivapirabu , Edirimanne Senarath 
Published: July 2023

Abstract
Local recurrence after mastectomy and autologous breast reconstruction is uncommon and tends to occur predictably within the superficial tissues or at the chest wall. We present a unique case of breast cancer recurrence involving the superficial and deep tissues. By parasitizing the pedicle of a free transverse rectus abdominis myocutaneous flap pedicle, the tumour was seen to extend through the chest wall to the right pleura.
Use of botulinum toxin as a non-surgical treatment option for idiopathic hallux varus: a case report
Authors: Gottlich Caleb , Murphy Alexandria , Jain Neil , Grimes Jerry 
Published: July 2023

Abstract
Hallux varus presents with midline deviation of the hallux at the first metatarsophalangeal joint. If left untreated, it may lead to pain and difficulty with normal daily activities. Here, we present a case of spontaneous hallux varus in an 84-year-old female treated non-operatively with injection of botulinum toxin in the Abductor Hallucis Brevis. Ultrasound guidance with electromyography was used to assist in all injections. Near total symptomatic relief and resumption of daily activities was obtained for up to 12 weeks at a time. Radiographic correction seen was improvement from 14° to 7° on weight bearing radiographs. After five rounds of treatment, no adverse reactions had been observed.
Battlefield Acupuncture as a Treatment Option for Chronic Tinnitus: A Pilot Study
Authors: Cesario Erin , Larionova Nicole , Scalo Julieta , Tepe Victoria , Esquivel Carlos , Spear Samuel A 
Published: July 2023

ABSTRACT

Introduction
There is no cure for tinnitus, which is a highly prevalent condition in service members and veterans. Battlefield acupuncture (BFA) can be used to manage pain and stress-related symptoms. We investigated BFA as a safe, low-cost treatment for tinnitus perception and coping in eight chronic tinnitus patients who were followed for 6 months after two BFA treatments to identify changes in tinnitus severity or impact.

Materials and Methods
Patients completed case history, Tinnitus Screener, Tinnitus Functional Index (TFI), Tinnitus Reaction Questionnaire (TRQ), and Hospital Anxiety and Depression Scale (HADS) questionnaires at baseline, at two BFA treatment sessions (2 weeks apart), and at four follow-up sessions (at 1, 2, 4 and 6 months after treatment). Questionnaire score changes were evaluated over time by using restricted maximum likelihood hierarchical regression modeling from baseline to 1-, 2-, 4-, and 6-month post-treatment follow-ups.

Results
TFI and TRQ group means were both significantly reduced at 1 month after treatment, and these reductions persisted through the 2- and 4-month follow-ups. The TRQ group mean remained significantly reduced after 6 months.

Conclusions
Findings from eight chronic tinnitus sufferers who received two BFA treatment sessions are reported here, suggesting at least short-term treatment benefits observed as reductions in tinnitus-related psychological distress and impact. Although these findings are constrained by the study’s small sample size and limited treatment period, its findings underscore the need for further research to determine the potential benefits of BFA for individuals who suffer from chronic tinnitus. Future research should consider the possibility of more lasting benefits through extended BFA treatment, with a comparison of BFA treatment against other treatment methods.
BurstDECONV: a signal deconvolution method to uncover mechanisms of transcriptional bursting in live cells
Authors: Douaihy Maria , Topno Rachel , Lagha Mounia , Bertrand Edouard , Radulescu Ovidiu 
Published: July 2023

Abstract
Monitoring transcription in living cells gives access to the dynamics of this complex fundamental process. It reveals that transcription is discontinuous, whereby active periods (bursts) are separated by one or several types of inactive periods of distinct lifetimes. However, decoding temporal fluctuations arising from live imaging and inferring the distinct transcriptional steps eliciting them is a challenge. We present BurstDECONV, a novel statistical inference method that deconvolves signal traces into individual transcription initiation events. We use the distribution of waiting times between successive polymerase initiation events to identify mechanistic features of transcription such as the number of rate-limiting steps and their kinetics. Comparison of our method to alternative methods emphasizes its advantages in terms of precision and flexibility. Unique features such as the direct determination of the number of promoter states and the simultaneous analysis of several potential transcription models make BurstDECONV an ideal analytic framework for live cell transcription imaging experiments. Using simulated realistic data, we found that our method is robust with regards to noise or suboptimal experimental designs. To show its generality, we applied it to different biological contexts such as Drosophila embryos or human cells.
Linking folding dynamics and function of SAM/SAH riboswitches at the single molecule level
Authors: Liao Ting-Wei , Huang Lin , Wilson Timothy J , Ganser Laura R , Lilley David M J , Ha Taekjip 
Published: July 2023

Abstract
Riboswitches are regulatory elements found in bacterial mRNAs that control downstream gene expression through ligand-induced conformational changes. Here, we used single-molecule FRET to map the conformational landscape of the translational SAM/SAH riboswitch and probe how co-transcriptional ligand-induced conformational changes affect its translation regulation function. Riboswitch folding is highly heterogeneous, suggesting a rugged conformational landscape that allows for sampling of the ligand-bound conformation even in the absence of ligand. The addition of ligand shifts the landscape, favoring the ligand-bound conformation. Mutation studies identified a key structural element, the pseudoknot helix, that is crucial for determining ligand-free conformations and their ligand responsiveness. We also investigated ribosomal binding site accessibility under two scenarios: pre-folding and co-transcriptional folding. The regulatory function of the SAM/SAH riboswitch involves kinetically favoring ligand binding, but co-transcriptional folding reduces this preference with a less compact initial conformation that exposes the Shine–Dalgarno sequence and takes min to redistribute to more compact conformations of the pre-folded riboswitch. Such slow equilibration decreases the effective ligand affinity. Overall, our study provides a deeper understanding of the complex folding process and how the riboswitch adapts its folding pattern in response to ligand, modulates ribosome accessibility and the role of co-transcriptional folding in these processes.
Dot1l cooperates with Npm1 to repress endogenous retrovirus MERVL in embryonic stem cells
Authors: Zhao Xin , Li Xiaomin , Sun Haiyang , Zhao Xuan , Gao Tingting , Shi Panpan , Chen Fuquan , Liu Lin , Lu Xinyi 
Published: July 2023

Abstract
Dot1l is a histone methyltransferase without a SET domain and is responsible for H3K79 methylation, which marks active transcription. In contradiction, Dot1l also participates in silencing gene expression. The target regions and mechanism of Dot1l in repressing transcription remain enigmatic. Here, we show that Dot1l represses endogenous retroviruses in embryonic stem cells (ESCs). Specifically, the absence of Dot1l led to the activation of MERVL, which is a marker of 2-cell-like cells. In addition, Dot1l deletion activated the 2-cell-like state and predisposed ESCs to differentiate into trophectoderm lineage. Transcriptome analysis revealed activation of 2-cell genes and meiotic genes by Dot1l deletion. Mechanistically, Dot1l interacted with and co-localized with Npm1 on MERVL, and depletion of Npm1 similarly augmented MERVL expression. The catalytic activity and AT-hook domain of Dot1l are important to suppress MERVL. Notably, Dot1l-Npm1 restricts MERVL by regulating protein level and deposition of histone H1. Furthermore, Dot1l is critical for Npm1 to efficiently interact with histone H1 and inhibit ubiquitination of H1 whereas Npm1 is essential for Dot1l to interact with MERVL. Altogether, we discover that Dot1l represses MERVL through chaperoning H1 by collaborating with Npm1. Importantly, our findings shed light on the non-canonical transcriptional repressive role of Dot1l in ESCs.
Set Up to Fail? Barriers Impeding Resident Communication Training in Neonatal Intensive Care Units
Authors: Cheng Anita , Molinaro Monica , Ott Mary , Cristancho Sayra , LaDonna Kori A. 
Published: July 2023

Purpose
Learning to navigate difficult clinical conversations is an essential feature of residency training, yet much of this learning occurs “on the job,” often without the formative, multisource feedback trainees need. To generate insight into how on-the-job training influences trainee performance, the perspectives of parents and health care providers (HCPs) who engaged in or observed difficult conversations with Neonatal Intensive Care Unit (NICU) trainees were explored.

Method
The iterative data generation and analysis process was informed by constructivist grounded theory. Parents (n = 14) and HCPs (n = 10) from 2 Canadian NICUs were invited to participate in semistructured interviews informed by rich pictures—a visual elicitation technique useful for exploring complex phenomena like difficult conversations. Themes were identified using the constant comparative approach. The study was conducted between 2018 and 2021.

Results
According to participants, misalignment between parents’ and trainees’ communication styles, HCPs intervening to protect parents when trainee-led communication went awry, the absence of feedback, and a culture of sole physician responsibility for communication all conspired against trainees trying to develop communication competence in the NICU. Given beliefs that trainees’ experiential learning should not trump parents’ well-being, some physicians perceived the art of communication was best learned by observing experts. Sometimes, already limited opportunities for trainees to lead conversations were further constricted by perceptions that trainees lacked the interest and motivation to focus on so-called “soft” skills like communication during their training.

Conclusions
Parents and NICU staff described that trainees face multiple barriers against learning to navigate difficult conversations that may set them up to fail. A deeper understanding of the layered challenges trainees face, and the hierarchies and sociocultural norms that interfere with teaching, may be the start of breaking down multiple barriers trainees and their clinician supervisors need to overcome to succeed.
The Sanders Classification and Obesity: Do Obese Kids With AIS Present With More Advanced Skeletal Maturity?
Authors: Henstenburg Jeffrey , Heard Jeremy , Jaynes Lance , Gnam Ashley , Laughter Kirk , Townsend Will , Smyly Aubrey , Sukkarieh Hamdi , Shah Suken A. , Brooks Jaysson T. , McDonald Tyler C. 
Published: July 2023

Introduction:
Obese and overweight (OOW) patients with adolescent idiopathic scoliosis (AIS) have been shown to initially present with a more advanced Risser score compared to normal weight (NW) patients. The Sanders Maturity Scale (SMS) is now more commonly used by surgeons to assist with treatment decisions because it more reliably predicts skeletal maturity. However, the relationship between SMS and obesity has not been described. We hypothesize that in patients with AIS, OOW patients will have a higher SMS score on initial presentation when compared to NW patients.

Methods:
Billing data from 2 different institutions were used to identify patients with AIS presenting to a pediatric orthopaedic spine surgeon for an initial visit between July 2012 and March 2020. We excluded those without height/weight data, spine radiographs, or left-hand radiographs for measuring SMS stage. Body mass index-for-age percentiles were calculated and used to group patients into NW (<85th percentile) or OOW (85th percentile and above) per Centers for Disease Control guidelines. After collecting preliminary data, a power analysis was performed using average SMS scores between NW and OOW patients with an alpha of 0.5, determining a needed sample size of approximately 300 male and 300 female subjects.

Results:
Five hundred ninety patients (296 female, 294 male) were identified. The SMS stage at presentation was significantly greater in OOW compared to NW patients for both females (5.9±1.8 vs. 5.2±1.7; P=0.003) and males (4.9±1.9 vs. 4.1±1.8; P=0.002). The major curve magnitude for OOW females was significantly different from NW females (36±16 degrees vs. 30±16 degrees; P=0.004). The major curve magnitude was not different for OOW and NW males (P=0.3).

Conclusion:
At initial presentation, OOW patients present at a greater skeletal maturity as measured by the SMS compared with NW patients. OOW female patients present with a greater major curve magnitudes than NW female patients. These results highlight negative implications of the pediatric obesity epidemic as it relates to the AIS population. These findings can be used to counsel families and provide anticipatory guidance for the AIS treatment plan.

Level of Evidence:
Level III—cross-sectional study.
Does Posterior Cord Compression From the Ligamentum Flavum Influence Clinical Outcomes After Anterior Cervical Discectomy and Fusion?
Authors: Lee Dong-Ho , Hwang Chang Ju , Cho Jae Hwan , Cho Sung Tan , Nam Hyun Wook , Park Sehan 
Published: July 2023

Study Design.
Retrospective cohort study.

Objective.
To clarify whether outcomes of anterior cervical discectomy and fusion (ACDF) differ according to the presence of posterior cord compression from the ligamentum flavum (CCLF)

Summary of Background Data.
Although ACDF effectively addresses anterior cord compression from disc material and bone spurs, it cannot address posterior compression. Whether ACDF could result in favorable outcomes when CCLF is present remains unclear.

Patients and Methods.
A total of 195 consecutive patients who underwent ACDF and were followed up for >2 years were included. CCLF was graded based on magnetic resonance imaging findings. Patients with CCLF grade 2 were classified as such, whereas patients with CCLF grades 0 to 1 were classified as the no-CCLF group. Patient characteristics, cervical sagittal parameters, neck pain visual analog scale, arm pain visual analog scale, and Japanese Orthopedic Association (JOA) score were assessed. Categorical variables were analyzed using a χ2 test, whereas continuous variables were analyzed using the Student t test. Multivariable logistic regression analysis was performed to elucidate factors associated with JOA recovery rates of >50%.

Results.
One hundred sixty-seven patients (85.6%) were included in the no-CCLF group, whereas the remaining 28 patients (14.4%) were included in the CCLF group. Among patients in the CCLF group, 14 patients (50.0%) achieved clinical improvement. JOA score significantly improved in the no-CCLF group after the operation (P < 0.001), whereas improvement was not appreciated in the CCLF group (P = 0.642). JOA scores at 3 months (P = 0.037) and 2 years (P = 0.001) postoperatively were significantly higher in the no-CCLF group. Furthermore, the JOA recovery rate at 2 years after surgery was significantly higher in the no-CCLF group (P = 0.042). Logistic regression demonstrated that CCLF was significantly associated with a JOA recovery rate of >50% at 2 years after surgery (odds ratio: 2.719; 95% CI: 1.12, 6.60).

Conclusion.
ACDF performed for patients with CCLF grade 2 showed inferior JOA score improvement compared with those with CCLF grade 0 or 1. ACDF cannot remove posterior compressive structures, which limits its utility when ligamentum flavum significantly contributes to cord compression.
Updating the Fitzpatrick Classification: The Skin Color and Ethnicity Scale
Authors: Coleman William , Mariwalla Kavita , Grimes Pearl 
Published: July 2023

BACKGROUND
There has been a significant increase in submissions to scientific journals addressing a broad spectrum of medical and surgical conditions in subjects grouped under the classification of “Skin of Color.” Authors, reviewers, and editors have struggled with accurate terminology.

OBJECTIVE
To update the Fitzpatrick scale to make it more accurate in stratifying various shades of skin color.

MATERIALS AND METHODS
A thorough literature review was performed using PubMed and Embase to assess existing skin color scales, and an extensive internet search was conducted using makeup foundation ranges as a starting point for skin tone matching.

RESULTS
The research resulted in a consensus that Fitzpatrick types 4 and 5 ratings were the most confusing in that these included a broad range of skin types with different responses to solar radiation, lasers, surgery, and cosmetic products. The authors reached a consensus that subdividing skin types 4 and 5 into “A” and “B” better defined them. The new scale that resulted was labeled the SCE scale (for Skin Color Ethnicity).

CONCLUSION
This new updated SCE scale should assist authors in better reporting scientific data in skin of color.
Association of the L3MBTL3 rs1125970 and rs4897367 Gene Polymorphisms With Coronary Heart Disease Susceptibility in the Chinese Population: A Case–Control Study
Authors: Li Yongdong , Zhang Jiaqiang , He Jun , Chen Xiaoyu , Zhang Xianbo , Wu Haiqing , Ding Yipeng 
Published: July 2023

Abstract:
Coronary heart disease (CHD) is a prevalent heart disease with high incidence and mortality rates worldwide, and its pathogenesis is related to genetic factors. L3MBTL3 has been reported to be potentially linked to CHD susceptibility. This study aims to explore the correlation between L3MBTL3 single nucleotide polymorphisms (SNPs) and CHD risk in the Chinese population. Three SNPs (rs1125970 A/T, rs4897367 T/C, and rs2068957 A/G) in L3MBTL3 from 649 patients with CHD and 649 healthy controls were genotyped using the Agena MassARRAY platform. The relationship between SNPs and CHD risk was evaluated by logistic regression analysis. Our study indicated that rs1125970 (TT: odds ratio [OR] = 0.76, P = 0.014) and rs4897367 (TT: OR = 0.74, P = 0.021) were related to a decreased susceptibility to CHD. Stratified analyses showed that rs1125970 could reduce the risk of CHD in males, subjects aged <60 years, with a body mass index <24 kg/m2, and nonhypertensive patients. rs4897367 exerted a risk-decreasing influence on CHD in nondiabetic patients. In the haplotype analysis, individuals with the Trs4897367Ars2068957 haplotype were less likely to develop CHD (OR = 0.74, P = 0.024). In summary, L3MBTL3 rs1125970 and rs4897367 were significantly correlated with a decreased susceptibility to CHD in the Chinese population.
Inclisiran and cardiovascular events: a comprehensive review of efficacy, safety, and future perspectives
Authors: Mohamed Ahmed A. , Ray Kausik K. 
Published: July 2023

Purpose of review
This review aims to offer an up-to-date evaluation of Inclisiran's (a small interfering RNA treatment) ability to decrease low-density lipoprotein cholesterol (LDL-C), as well as its safety and potential effects on decreasing cardiovascular risk.

Recent findings
Inclisiran significantly lowers LDL-C levels, as shown by phase III studies, by inhibiting hepatic synthesis of proprotein convertase subtilisin kexin 9 (PCSK-9), a protein implicated in the degradation of LDL receptors. Inclisiran has the benefit of subcutaneous injection twice a year, which may reduce patient nonadherence when compared with other LDL-C reducing therapies such as statins and ezetimibe, which require daily dosing. When added on top of statins, a greater proportion of patients achieved recommended cholesterol goals. It has also demonstrated a good safety profile with few adverse effects.

Summary
Inclisiran is a promising treatment for lowering LDL-C levels in people at high risk of atherosclerotic cardiovascular disease. It is a practical and well tolerated option for those who struggle to stick to medication regimes because of its twice-yearly dosage schedule and a good safety profile. Although it has been demonstrated to be effective in decreasing LDL-C, further research is needed to determine its impact on reducing cardiovascular events. Nonetheless, Inclisiran is a significant advancement in lipid-lowering medication and could improve patient outcomes.