bluuebunny/crossref_metadata_2025 huggingface dataset:
The Second Message of Islam
Authors: Taha Mahmoud Mohamed
Published: November 2024

Mahmoud Mohamed Taha (Sudan, circa 1910-1985) received his university degree in Khartoum, Sudan, and worked for many years as a civil engineer, specializing in irrigation. At the same time, he was active in the Sudanese independence movement. In 1945, he helped to found the Republican Party and then spent several years in jail as a result of his activism. After independence, his followers founded the Republican Brothers, which Taha led until his execution in 1985. The founding document of this organization, first drafted in the early 1950s and published in 1967-excerpted here-presents Taha’s unorthodox view that the earlier Qur’anic revelations (revealed in Mecca before the Prophet gained political power) should be granted greater importance than the later revelations, which refer more narrowly to the conditions of the Prophet’s rule in Medina. This view brought Taha into conflict with the Sudanese government’s implementation of more orthodox Islamic laws in the 1980s. His protest against these policies led to his arrest and execution.
European Economic and Environmental Constitutionalism as Driver for UN and WTO Sustainable Development Reforms
Authors: Petersmann Ernst-Ulrich
Published: November 2024

The Introduction recalls why the progressive transformation of European economic integration law into European community and constitutional law remains the most successful example for using regional law and jurisprudence for promoting also global community law. Section II explains why the increasing authoritarian and neoliberal rejection of “transnational constitutionalism” (like judicial protection of transnational rule-of-law) undermines collective protection of global public goods demanded by citizens. Section III describes how Europe’s multilevel democratic constitutionalism continues to enable the European Union to exercise leadership for UN and WTO legal reforms such as compulsory WTO arbitration and international emission trading systems aimed at mitigating climate change by reducing carbon emissions. Section IV uses the examples of competing internet regulations in China, Europe, and the United States, and of international criminal law (like the arrest warrant of the International Criminal Court against Russian President Putin), for explaining the limits of constitutional and institutional restraints on UN and WTO governance.
Russian Crimes Against Humanity in Ukraine
Authors: Beres Louis René
Published: November 2024

Ongoing Russian crimes against humanity in Ukraine are overwhelming and intersecting. Defined at the Charter of the International Military Tribunal (Aug. 8, 1945, Art. 6(c), 59 Stat. 1544, 1547, 82 U.N.T.S. 279, 288), these crimes underscore the continuing futility of “Westphalian” international law. Nonetheless, for the foreseeable future, realpolitik will remain the tangible geo-strategic context for operational international law, and new ways will still be needed to reconcile core normative obligations with particular state practice. In the final analysis, there can be no narrowly technical solutions to aggression and genocide, only functional legal mechanisms based on planetary interdependence and human “oneness.” To prevent future crimes against humanity of the sort being brought about by Vladimir Putin, our continuously fragile system of international law will need to be based more openly upon immutable connections between macrocosm (world legal order) and microcosm (individual human being).
Guilty Consciences and Making Good
Authors: Neff Stephen C.
Published: November 2024

The law of reparation has the curious feature of requiring automatic and unilateral action on the part of wrongdoers, without regard to whether there is a claim for redress by the victim party. This contribution points out historical and conceptual roots of this idea. Early traces are found in ancient Greece, in the philosophy of Plato. In medieval Europe, the penitential system of the Catholic Church placed a heavy stress on the unilateral duty of restitution by wrongdoers, notably in the areas of usury and of the waging of unjust wars. These ideas were substantially adopted by the pioneer writers on international law in the seventeenth century, Francisco Suárez and Hugo Grotius. In state practice, there is evidence of a general duty of reparation in the peace-treaty practice of states in the nineteenth and early twentieth centuries. A number of these treaties made specific provision for monetary payments for identified past actions. Modern doctrine on the subject came first from August Heffter. The principal writer on the subject was the Italian scholar and judge Dionisio Anzilotti, with Hans Kelsen as a dissenter. Anzilotti’s views have been substantially adopted by the World Court, as well as by the International Law Commission in its Articles on State Responsibility of 2001.
International Centre for Settlement of Investment Disputes (ICSID)
Authors: Reinisch August , Tropper Johannes
Published: November 2024

The 2022/2023 jurisprudence of ICSID tribunals and ad hoc committees addressed among others the jurisdictional issues of the notions of “investment” and “investor” under Article 25 ICSID Convention, consent to jurisdiction via domestic legislation, the so-called intra-EU objection to jurisdiction, the interplay between corruption and the admissibility of claims, and narrow dispute settlement clauses. Prominent procedural issues concerned the dismissal of claims manifestly without legal merit and provisional measures related to domestic proceedings. On the merits, 2022 and 2023 cases primarily dealt with expropriation, fair and equitable treatment, and the scope of the umbrella clause. On quantum, some tribunals addressed the appropriate standard of compensation in cases involving non-expropriation claims and the discounted cash flow method for calculating damages in great detail. Annulment committees addressed the limited grounds for annulling awards under the ICSID Convention emphasizing that the annulment procedure was no appeals procedure.
International Criminal Court (ICC)
Authors: Alexander Knoops Geert-Jan , Desevedavy Alexandre
Published: November 2024

The International Criminal Court (ICC) encountered a notable surge in activities from 2022 to 2023, with multiple cases advancing to trial and new investigations initiated. This overview explores key themes in the Court’s jurisprudence and activities, focusing on cooperation, case consolidation, and procedural rule interpretation. Fair trial issues, detention reviews, and defense team rights were addressed. Additionally, it delves into three investigations, including the probe into Ukraine. The summary examines the intensive activity within the ICC during 2022–2023, highlighting specific cases like Abd-Al-Rahman (Sudan), Yekatom and Ngaïssona and Said (Central African Republic), Ongwen and Kony (Uganda), Al Hassan (Mali), and updates on the Gicheru, Blé Goudé, and Ntaganda cases. Each case’s legal proceedings, decisions, and developments are detailed. It also explores investigations by the Office of the Prosecutor in the Republic of the Philippines, Venezuela, and Ukraine, discussing legal proceedings, challenges, and ICC decisions. Notably, the Ukraine situation and arrest warrants for alleged war crimes and crimes against humanity are addressed, along with debates on establishing a special tribunal and challenges related to the crime of aggression.
Permanent Court of Arbitration (PCA)
Authors: Teles Patrícia Galvão , Antunes João Gil
Published: November 2024

The Permanent Court of Arbitration (PCA) is the oldest inter-governmental organization dedicated to the peaceful settlement of international disputes. The PCA currently administers over two hundred cases involving such subjects as inter-state territorial and maritime boundaries, the interpretation and application of international treaties, inter-governmental organizations, international environmental law, human rights, foreign investment, and international commercial transactions. In 2022, the arbitral tribunal in PCA Case No. 2019-28 in the matter of an arbitration before an arbitral tribunal constituted under Annex VII to the 1982 UN Convention on the Law of the Sea between Ukraine and the Russian Federation in respect of a Dispute concerning the Detention of Ukrainian Naval Vessels and Servicemen rendered the award in which it addressed the jurisdictional objections raised by the Russian Federation. In this award, the arbitral tribunal dealt with relevant issues of international, including in the field of the law of the sea, in a very geopolitical sensitive context.
Eurasian Economic Union Court (EAEU Court)
Authors: Mikhaliova Tatsiana , Douhan Alena
Published: November 2024

This article presents an overview of the legal grounds of forming and functioning of the Court of the Eurasian Economic Union. The author discusses challenges, progressive or less successful results of its activity during the first nine years, which form the full cadence of the first Court’s composition, paying attention to the peculiarities of the competence and significance of the practice of the Court within the Eurasian region—the Eurasian Economic Union and its member states. An overview of the recent legal maxims is made for the selected case law of the Court in 2023, which develops main features of the Eurasian law.
European Court of Human Rights (ECtHR)
Authors: O’Leary Síofra
Published: November 2024

The period 2022–2023 was a very challenging but productive one for the European Court of Human Rights. The invasion of Ukraine by the Russian Federation dominated the landscape, leading to changes in the political and legal borders of the Council of Europe and rendering the Court’s work to uphold and protect human rights all the more indispensable. This contribution looks at sixteen Grand Chamber judgments handed down during the reference period. The relevant cases cover a wide variety of subject matter, including judicial reforms alleged to undermine judicial independence, sanctions on broadcasters in pursuit of media pluralism, procedures required in relation to requests for repatriation by nationals, and hate speech on social media. It also sheds light on four new advisory opinions adopted under Protocol No. 16 to the Convention. Moreover, the overview seeks to demonstrate how the impact case-processing strategy is working in practice, with a significant number of important Chamber judgments delivered throughout the reference period, some of which are also briefly presented.
Hybrid Tribunals
Authors: Williams Sarah
Published: November 2024

This contribution considers the practice of several hybrid tribunals—those tribunals with a mix of international and national law and personnel—in the period 1 January 2022 to 31 July 2023. The tribunals examined are: Extraordinary African Chambers (EAC); Special Tribunal for Lebanon (STL); Residual Mechanism for the Special Court for Sierra Leone (RSCSL); Extraordinary Chambers in the Courts of Cambodia (ECCC); Kosovo Specialist Chambers (KSC); and the Special Criminal Court in the Central African Republic. Several of these hybrid tribunals entered a residual phase during the period under consideration, while others commenced the judicial phase and issued their first trial and appellate judgments. Reparations remains an important issue for several institutions. Evident is the impact of a lack of sustainable funding and uncertain political support from key actors, in particular the host government. Despite these limits, the model remains a suggested option for other emerging contexts.
Mutation of GLR2 confers enhanced glufosinate resistance and salt tolerance in rice
Authors: Cheng Weimin , Ren Yan , Wang Jiayi , Chen Chunpeng , Fang Cheng , Peng Lingling , Zhang Dongyang , Tao Liangzhi , Zhan Yue , Wu Kun , Wu Yuejin , Liu Binmei , Fu Xiangdong , Ye Yafeng
Published: November 2024

The GLR2 transcription factor regulates glufosinate resistance and enhances abiotic stress tolerance in rice through interaction with the GLR1 transcription factor and modulation of gene expression.
Evaluation of genetic diversity and genome-wide association studies of resistance to bacterial wilt disease in potato
Authors: Okiro Lilian A. , Mulwa Richard M. , Oyoo Maurice E. , Okwiri Ojwang Pascal P. , Otieno Susan A. , Gaiero Paola , Pereira Guilherme da Silva , Mendes Thiago
Published: November 2024

The development of novel improved varieties adapted to unstable environmental conditions is possible through the genetic diversity of breeding materials. Potato is among the most important food crops worldwide, however, there are still significant hindrances to breeding gains attributed to its autotetraploid and highly heterozygous genome. Bacterial wilt caused by the Ralstonia solanacearum species complex (RSSC) is an important disease affecting potato among many economically important crops worldwide. No cultivated potato genotypes have shown a satisfactory level of resistance to bacterial wilt. Nevertheless, resistance can play a crucial role in effective integrated disease management. To understand the genetic landscape of bacterial wilt resistance in cultivated potato, we evaluated the diversity of 194 accessions from the International Potato Centre (CIP) using 9,250 single nucleotide polymorphisms (SNPs) and their associations to the response to bacterial wilt disease evaluated over two independent trials. Twenty-four accessions showed high resistance throughout both trials. Genetic diversity analysis revealed three major clusters whose subgroups were mostly represented by CIP clones derived from common parents. Genome-wide association analyses have shown six major hits: two on chromosome 8, and one on each chromosome 2, 4, 5, and 9. These results facilitate genetic dissection of bacterial wilt resistance and marker-enabled breeding in elite genotypes for potato breeding initiatives.
Which Scoring System Best Predicts Long-term Survival in Patients with Spinal Metastasis in the Era of Targeted Systemic Treatment? A Comparative Study of Eight Prognostic Models
Authors: Kang Dong-Ho , Park Jin-Sung , Kang Minwook , Jung Kyunghun , Lee Chong-Suh , Park Se-Jun
Published: November 2024

Study Design.

Retrospective observational study.

Objective.

To evaluate the accuracy of eight scoring systems, including the Tomita, modified Tokuhashi, modified Bauer, Rades, Oswestry Spinal Risk index (OSRI), Lei, New England Spinal Metastasis Score, and Skeletal Oncology Research Group (SORG) nomogram, for predicting long-term survival of patients with spinal metastasis.

Summary of Background Data.

Predicting the prognosis of spinal metastasis is vital for surgical decisions, yet the effectiveness of existing scoring systems in identifying long-term survival remains unclear.

Methods.

456 cases were finally included. Prognostic scores were compared with survival outcomes. Receiver operating characteristic (ROC) curves were analyzed for the entire cohort and across three distinct time periods to evaluate the area under the curve (AUC) for 1-year and 2-year survival, alongside Harrell’s C-statistic.

Results.

The mean patient age was 58.9 years, and the median survival time was 8.6 months. For the entire cohort, the SORG nomogram, OSRI, and modified Tokuhashi scores yielded Harrell’s C-index values of 0.64, 0.63, and 0.62, respectively. For 1-year survival prediction, the SORG nomogram, OSRI, and modified Tokuhashi score demonstrated moderate discriminative power, with AUC values of 0.72, 0.71, and 0.70, respectively. Similarly, for 2-year survival prediction, the modified Tokuhashi score, SORG nomogram, and OSRI also revealed moderate discriminative power, with AUC values of 0.73, 0.72, and 0.70, respectively. For patients who underwent surgery in the most recent period, OSRI demonstrated the highest predictive accuracy for 1-year survival, with a Harrell’s C-index of 0.63 and an AUC of 0.68, and 2-year survival, with a Harrell’s C-index of 0.63 and an AUC of 0.64.

Conclusion.

Most scoring systems exhibited low discriminative power, with only the SORG nomogram, OSRI, and modified Tokuhashi scores demonstrating moderate power for predicting long-term survival. In the most recent period, the OSRI demonstrated the highest predictive accuracy for both 1-year and 2-year survival.
Prevalence of human papilloma virus in head and neck mucous squamous cell carcinoma and genotypes by location: an observational study
Authors: Uhlrich Emilie , Klijanienko Jerzy , Martin Joey , Jeannot Emmanuelle , Vincent-Salomon Anne , Freneaux Paul , Le Tourneau Christophe , Choussy Olivier , Dubray-Vautrin Antoine
Published: November 2024

Human papillomavirus (HPV) is a factor in oropharyngeal cancer, but data regarding other head and neck locations are scarce in France. The main objective of the study was to determine the prevalence of HPV in head and neck cancers at all locations. As a secondary objective, we aimed to investigate the HPV genotypes. We retrospectively included in a tertiary center between 2014 and 2020 mucosal squamous cell carcinomas of the head and neck in adult. First outcome was the prevalence of HPV cancer. Secondary outcomes were overall survival (OS) at 2 and 5 years and disease-free survival (DFS). A total of 508 patients were enrolled, resulting in 537 cases of mucous squamous cell carcinoma of the head and neck (n = 29 synchronous carcinomas). Clinical, pathological, and survival data were collected, and a double PCR for HPV with genotyping was performed on most of the samples. The HPV prevalence in the cohort was 28.2%, with HPV 16 being the predominant genotype (87%). However, HPV-positive status did not significantly improve OS at 2 and 5 years or DFS (P = 0.1, P = 0.64, and P = 0.07, respectively). It was also observed that HPV-positive patients had significantly fewer second tumor localizations (P < 0.01). The prevalence of HPV continues to rise, and the complexities surrounding HPV status and its association with clinical outcomes in head and neck squamous cell carcinoma highlight the impact of vaccination.
Histopathologic Perspective of Nail Lichen Planus: A 10-year Case Series From a Tertiary Care Center in South India
Authors: Fernandez Ashrita Laura , Bukelo Maria Frances , Bhat Pernaje Ishwara , Kalegowda Inchara Yeliur
Published: November 2024

Nail involvement is seen in 10% of lichen planus patients, with a subset developing severe destruction of the nail matrix. Nail biopsy is a complex procedure usually done when nails are the only site of involvement. The pathology of nail lichen planus (NLP) has been the subject of very few studies. Most studies refer to the major and minor histopathologic criteria proposed by Hanno et al. This study aims to characterize the histopathologic features of NLP. Twenty five patients of NLP with nail biopsies, diagnosed in the last 10 years were included in the study. Lichen planus was suspected in all patients, and the alternative diagnosis was psoriasis/onychomycosis and melanoma. On histopathology, the common features included acanthosis (88%), lichenoid lymphocytic inflammation (96%), and hypergranulosis (72%). Detachment of epithelium from the subepithelium, a hitherto unreported feature, was noted in 60% of cases. Less common features were lymphocytic exocytosis (48%), melanophages (40%), basal vacuolar alteration (24%), apoptotic keratinocytes (28%), fraying of the nail plate (24%), and spongiosis (20%). Understanding the common and less common histopathologic features and their correlation with clinical findings is essential to diagnose NLP accurately rather than stressing histologic criteria as major/minor, which may lead to the underdiagnosis of cases.
Negative Pressure Wound Therapy with Instillation for Periprosthetic Infection after Breast Reconstruction: A Systematic Review
Authors: O’Connor Madeline J. , Huffman Kristin N. , Ho Kelly , Marzouk Sammer , Casas Fuentes Rolando J. , Zhang Kenneth L. , Melnick Bradley A. , Sparks Payton J. , Harris Raiven , Bartler Angelica V. , Collinsworth Ashley , Griffin Leah , Galiano Robert D.
Published: November 2024

Background:

Periprosthetic infection after breast reconstruction is not uncommon and can result in loss of the implant pocket and negative patient outcomes. Management of these infections typically involves removal of the prosthesis, treatment with antibiotics, and delayed reconstruction upon infection resolution. The impact of adjunctive use of negative pressure wound therapy with instillation and dwell (NPWTi-d) on breast pocket salvage rates, time to implant reinsertion, and related outcomes was examined.

Methods:

A systematic literature search using PubMed, Cochrane, OVID, Scopus, and Embase was conducted to identify peer-reviewed articles written in English and published between January 2004 and April 2023 that examined NPWTi-d use in the breast pocket with a history of periprosthetic infection after breast reconstruction.

Results:

Of the 1703 publications, 6 studies met inclusion criteria, representing 115 patients and 122 breasts. The overall breast pocket salvage rate with NPWTi-d across studies was approximately 92%. In the 6 studies that included prosthesis type and radiation history, overall salvage rates were 97.8% (45 of 46) for pockets containing implants and 93.8% (15 of 16) for pockets containing tissue expanders. Salvage rates were 85.7% (12 of 14) and 91.7% (53 of 58) for irradiated and nonirradiated breasts, respectively. Mean time to implant reinsertion ranged from 2.3 to 10.3 days.

Conclusions:

In this review, antibiotic therapy along with adjunctive use of NPWTi-d for periprosthetic infections after breast reconstructions was associated with high rates of breast pocket salvage and reduced time to implant reinsertion. Larger prospective and randomized trials are needed to better understand and optimize the effectiveness of NPWTi-d in this population.
Novel, Low-cost Ear Elevation Splint for Auricular Construction
Authors: Chwa Emily S. , Baltrusch Breanna , Claussen Erin , Allison Sophia , Shah Nikhil D. , Yamada Akira
Published: November 2024

Modern approaches to autogenous auricular reconstruction involve a multistage approach where ear elevation is an independent procedure. The goal is to project the reconstructed ear at an anatomically accurate and symmetric auriculocephalic angle, but postoperative scar contraction may adversely affect the long-term outcomes. An ear elevation splint was developed to provide rigid support for the auricle during the acute healing period to promote lasting elevation. The splint is low cost, made from commonly used orthotic materials, and can be conveniently customized for each patient in less than 15 minutes.
Spotlight on Amniotic Membrane Extract Eye Drops: A Review of the Literature
Authors: Kilian Raphael , Bonacci Erika , Donner Ruth , Lammer Jan , Rizzo Clara , Crincoli Emanuele , De Ruvo Valentino , Schmidinger Gerald , Pedrotti Emilio , Marchini Giorgio
Published: November 2024

Objective:

To review the literature focusing on the effectiveness of amniotic membrane extract eye drops (AMEDs) in the treatment of ocular surface diseases.

Methods:

PubMed/MEDLINE, Scopus, and CENTRAL databases were searched until March 4, 2024. Overall, we identified 1,121 studies, 26 of which were selected for a full-text review. Twelve studies met the inclusion criteria and were analyzed for clinical improvements, time to resolution of corneal staining, adverse events, and preparation methods. Strength of clinical data was graded according to the Oxford Center for Evidence-Based Medicine.

Results:

Overall, AMED compounds were used in 296 eyes of 205 patients. Fifty-nine percent of eyes were treated for dry eye disease, 23% for an epithelial defect, and the rest (18%) for other corneal wound healing disorders. Three main types of eye drops preparation were described, that is, lyophilized, homogenized, and fresh AMED. Although the methods of outcome reporting were heterogeneous, all included studies showed various grades of improvement in both signs and symptoms. The overall incidence of ocular side effects was 2.3%.

Conclusions:

Despite the suboptimal quality of evidence, overall, the available literature suggests that AMED is a valuable tool in the treatment of ocular surface disorders.
The radiosensitivity of niraparib tosylate to esophageal squamous cell carcinoma is stronger under hypoxia and higher-pressure conditions
Authors: Wang Hongmin , Zhang Fuxia , Zhao Yingying , Wang Yongtao , Xin Chao , Cui Yuzhong
Published: November 2024

Background:

Radiotherapy is an effective method for esophageal squamous cell carcinoma (ESCC) treatment show reduced effectiveness in long-term due to reduced sensitivity of cancer cells to radiotherapy. Niraparib tosylate, a poly ADP-ribose polymerase (PARP) inhibitor may enhance the radiosensitivity of these cells. Hence, the present study was aimed to study the effects of niraparib tosylate on ESCC proliferation, apoptosis and cell cycle along with radiosensitivity enhancement efficiency.

Materials and methods:

ESCC cell lines, KYSE-30 were subjected to niraparib tosylate or irradiation treatments or combination of both. CCK8 and colony formation assays were performed to monitor cell growth status. Cell cycle and apoptosis level were investigated through flow cytometry. The expressions of targeted genes were detected at protein levels by western blot. Besides, xenografts were successfully established in immunocompromised mice. Student’s t-test was used to compare data and P < 0.05 was considered statistically significant.

Results:

Treatment with niraparib tosylate showed G2/M cycle arrest and apoptosis in KYSE-30 cells and the rate was observed to be more significant with combination therapy. These effects were further strengthened when cells were cultured under hypoxia and high atmospheric pressure. An enhanced susceptibility to radiotherapy was observed with niraparib tosylate combination. The homologous recombination related regulator, Rad51, showed remarkable upregulation in cancer cells exposed to combination of drug-radiation treatment. The tumor burden was also relieved in xenograft mouse models with combination of drug-radiation treatment, indicating the potential of niraparib tosylate use clinical cancer therapy.

Conclusion:

From the results, a novel function of niraparib tosylate can be established, impairing DNA damage repair efficiency to increase the susceptibility of ESCC to radiotherapy, resulting in cell apoptosis and G2/M cycle arrest in vitro and in vivo.
Collaborative care models in adult congenital heart disease transplant
Authors: Kearney Katherine , McDonald Michael , Roche Lucy
Published: November 2024

Purpose of review

While multidisciplinary collaboration is a tenant of quality heart failure care and critical to the success of transplant programs, this essay challenges the temptation to shoehorn adult congenital heart disease (ACHD) patients into preexisting processes and paradigms. We explore the development of more relevant models, purposefully designed to improve ACHD transplant volumes and outcomes.

Recent findings

Globally, the rapid acceleration of ACHD patients living with and dying from HF stands in stark contrast to their access to transplant. Inferior early outcomes after ACHD transplant remain an undeniable barrier. And yet while all large registry datasets attest to this statistic, a few centers have achieved results comparable to those in acquired heart disease. This despite increases in both ACHD candidate complexity and referrals for Fontan Circulatory Failure. Perhaps something in their approach to care delivery is key?.

Alone, neither ACHD nor transplant programs can provide optimal management of HF in ACHD. A siloed approach is similarly inadequate. Building new ACHD-HF-Transplant teams, centered on the patient and supplemented by ad hoc expert partnerships, is an exciting approach that can improve outcomes, create a high-quality training environment, and in our experience, is a truly rewarding way of working together.
Familial Mediterranean Fever in Pregnancy
Authors: Davidson Alana , Kuller Jeffrey A. , Dotters-Katz Sarah K. , Wood Rachel L.
Published: November 2024

Importance

Though the incidence of familial Mediterranean fever (FMF) in pregnancy is rare, understanding the etiology and symptomatology of FMF is essential for obstetric treatment of patients with FMF.

Objective

Familial Mediterranean fever is a hereditary periodic fever syndrome that has unique obstetric considerations. Familial Mediterranean fever is typically characterized by recurrent episodes of high-grade fevers, pleuritis/pericarditis, and arthritis lasting 1–3 days with complete recovery seen in between episodes. Familial Mediterranean fever is seen worldwide, but particularly in patients of Mediterranean descent. Its incidence varies across ethnicities.

Evidence Acquisition

This article provides a comprehensive review of existing literature.

Results

It is well established that colchicine is safe and effective to use during pregnancy in patients with FMF to control and prevent flares. Although most pregnancies progress without negative outcomes, FMF has been shown in the literature to be associated with preterm birth and premature rupture of membranes. Its impact on increasing the rate of fetal growth restriction and hypertensive disorders is less understood. Additionally, FMF flares may be suppressed in pregnancy, whereas other sources report that flares are similar to those outside of pregnancy in terms of frequency, type of symptoms, and severity. Breastfeeding is safe in patients with FMF who are taking colchicine. Genetic counseling can be offered to patients with FMF, but in utero diagnostic testing is generally not pursued solely for the indication of FMF diagnosis in the fetus.

Conclusions and Relevance

Further investigation of the impact of FMF on pregnancy is needed for advancing our understanding of the condition and optimizing care for pregnant individuals with FMF.

Target Audience

Obstetricians and gynecologists, family physicians.

Learning Objectives

After reading this review, the provider will be better able to describe the clinical significance and impact of FMF in pregnancy; explain the incidence, pathophysiology, diagnostic criteria, and treatment of FMF; and discuss genetic testing in the setting of a FMF diagnosis.
Contraceptive Strategies for Reducing the Risk of Reproductive Cancers
Authors: Aliabadi A. R. , Wilailak Sarikapan , McNally Orla , Berek Jonathan S. , Sridhar Aparna
Published: November 2024

(Abstracted from Int J Gynaecol Obstet 2024;166(1):141–151)

Reproductive cancers include endometrial cancer, ovarian cancer, cervical cancer, and gestational trophoblastic neoplasia and represent a significant health burden across geographic locations and age groups, although there is evidence that some contraceptive methods can be protective against certain types of malignancies. This article is a review aimed to express the disease burden of different reproductive cancers as well as known evidence of contraceptives in the prevention and management of these diseases.
Maternal Hybrid Immunity and Risk of Infant COVID-19 Hospitalizations: National Case-Control Study in Israel
Authors: Guedalia Joshua , Lipschuetz Michal , Cahen-Peretz Adva , Cohen Sarah M. , Sompolinsky Yishai , Shefer Galit , Melul Eli , Ergaz-Shaltiel Zivanit , Goldman-Whol Debra , Yagel Simcha , Calderon-Margalit Ronit , Beharier Ofer
Published: November 2024

(Abstracted from Nat Commun 2024;15:2846)

Infants with COVID-19, especially the Omicron variant, are at increased risk of acute respiratory failure and hospitalization. Pfizer and Moderna mRNA vaccines significantly reduce this risk but are not approved for infants under 6 months.
The Impact of COVID-19 on Patterns of Fractures Presenting to Pediatric Emergency Departments
Authors: Ruest Stephanie M. , Hanson Holly R. , Kiragu Andrew , Lee Lois K. , Zonfrillo Mark R. , Pomerantz Wendy J.
Published: November 2024

Objective

To examine differences in pediatric fracture prevalence, severity, and mechanisms of injury before and during the COVID-19 pandemic.

Methods

This is a subanalysis of data from a multicenter, cross-sectional study of all injury-related visits to 40 urban pediatric emergency departments (EDs) for children younger than 18 years occurring January 2019–December 2020. ED visits for injuries including fractures were identified by International Classification of Diseases, Tenth Revision codes. Comparative analyses of patient demographics, fracture prevalence, severity, and mechanisms of injury for March 17, 2019, to December 31, 2019 (pre-COVID), versus March 15, 2020, to December 31, 2020 (during COVID), were performed.

Results

Fracture-related visits comprised 21.0% (n = 123,684) of all injury visits (n = 589,083) during the study period. There were 16,190 fewer fracture-related visits (−23.2%) in 2020 than 2019. There were differences in the proportion of fracture-related visits by age (P < 0.0001), with increases in children younger than 5 years and decreases in children 5 to 18 years old. There were higher proportions of visits in 2020 among female patients, White children, non-Hispanic children, and those with private insurance (P < 0.0001, respectively). Patients with fractures in 2020 were more severely injured, with higher proportions of hospitalizations (P < 0.0001), intensive care unit admissions (P < 0.0001), deaths (P = 0.007), and higher injury severity scores (P < 0.0001). Fracture mechanisms shifted to more motor vehicle crashes, bicycles, and firearms in 2020 (P < 0.0001).

Conclusions

Despite a decrease in fracture-related visits to urban pediatric EDs during the early COVID-19 pandemic, there was an increase in the proportion of ED visits for children younger than 5 years and higher severity injuries. These findings highlight injury epidemiology pattern shifts that occurred during the pandemic. Identifying higher-risk populations for fracture may help guide targeted education and prevention efforts.
Estimated benefit of PCSK9 inhibition following ischemic stroke due to severe intracranial atherosclerosis
Authors: Siegler James E. , Goicoechea Elena Badillo , Yaghi Shadi , Morsi Rami Z. , Arevalo Andrea , Smith Matthew M. , Kothari Sachin , Desai Harsh , Sehgal Neha , Rana Rohini , Kellogg Caroline , Jhaveri Aditya , de Havenon Adam , Dunne Therese , Cameron Kamil , Chaturvedi Seemant , Ghannam Malik , Prabhakaran Shyam , Coleman Elisheva , Brorson James R. , Mehendale Rachel , Kass-Hout Tareq
Published: November 2024

Background

The risk of recurrent atherosclerotic vascular events in patients with stroke due to intracranial atherosclerotic disease (ICAD) is high. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) can dramatically lower low-density lipoprotein (LDL) levels when added to statins, but are not currently indicated for patients with ICAD.

Methods

In this secondary analysis of the SAMMPRIS trial, we estimated the association between LDL reduction (enrollment to day 30, by quartiles) and recurrent cerebral infarction or myocardial infarction (MI) beyond 30 days (primary outcome).

Estimates were assessed using adjusted Cox proportional hazards regression accounting for age, sex, race, Hispanic ethnicity, baseline LDL, vascular comorbidities, and statin use prior to enrollment. We applied relative LDL reduction estimates from PCSK9i trials to project adjusted incidence rate differences of the primary outcome observed in SAMMPRIS with an equivalent LDL reduction. Semiparametric Cox models estimated the annualized relative risk of primary events if PCSK9i were used in the SAMMPRIS population.

Results

Of the 451 patients from SAMMPRIS, 378 met inclusion criteria. By day 30, LDL levels fell significantly (absolute change -19mg/dL, IQR -41 to -2). In unadjusted Cox regression compared to the lowest quartile, patients in the highest quartile of LDL improvement trended toward a lower rate of the primary outcome (Q4 vs. Q1 hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.35-1.26), achieving significance after multivariable adjustment (adjusted HR 0.38, 95% CI, 0.16-0.89). Every 10 mg/dL improvement in 30-day LDL was associated with a 9% lower rate of the primary outcome (adjusted HR 0.91, 95% CI, 0.83-0.997). Assuming an average projected effect of PCSK9i, with half of SAMMPRIS patients having been treated, PCSK9i use could reduce the annualized risk of the primary outcome by 33.2%.

Conclusions

More aggressive LDL lowering in patients with stroke due to ICAD is associated with lower rates of recurrent stroke or MI, and this can be achieved with PCSK9i use.
Genomic characterization uncovers transmission dynamics of Marburg Virus in Rwanda following a single zoonotic spillover event
Authors: Butera Yvan , Mutesa Leon , Parker Edyth , Muvunyi Raissa , Umumararungu Esperance , Ayitewala Alisen , Musabyimana Jean Pierre , Olono Alhaji , Sesonga Placide , Ogunsanya Olusola , Kabalisa Emmanuel , Adedokun Oluwatobi , Gahima Nelson , Irankunda Laetitia , Mutezemariya Chantal , Niyonkuru Richard , Uwituze Arlene , Uwizera Ithiel , Kagame James , Umugwaneza Arlette , Rwabuhihi John , Umwanankabandi Fidele , Mbonitegeka Valens , Ntagwabira Edouard , Kayigi Etienne , Izuwayo Gerard , Murenzi Herve , Mukankwiro Therese , Tuyiringire Nasson , Uwimana Jean Marie Vianney , Gasengayire Agnes , Sindayiheba Reuben , Onyeugo Glory-Ugochi , Aragaw Merawi , Gitundu Lenny , Bigirimana Radjabu , Fallah Mosoka , Ejikeme Adaora , Sembuche Senga , Kabanda Alice , Mugisha Jean Claude , Siddig Francis Emmanuel Edwar , Gashema Pierre , Ndayisenga Jerome , Rugamba Alexis , Kanyabwisha Faustin , Murenzi Gad , Happi Anise , Ngabonziza Jean Claude Semuto , Gashegu Misbah , Ahmed Ayman , Bigirimana Noella , Rwagasore Edson , Semakula Muhammed , Rwabihama Jean Paul , Musanabaganwa Clarisse , Seruyange Eric , Nkeshimana Menelas , Twagirumugabe Theogene , Turatsinze David , Remera Eric , Gahamanyi Noel , Tessema Sofonias Kifle , Mukagatare Isabelle , Nsanzimana Sabin , Happi Christian , Muvunyi Claude Mambo
Published: November 2024

The ongoing outbreak of Marburg virus disease (MVD) in Rwanda marks the third largest historically, though it has exhibited the lowest fatality rate. Genomic analysis has identified a lineage with limited internal diversity most closely related to a genome sequence from a sporadic case sampled in 2014 in Uganda, though the lineages have diverged from a common ancestor that was circulating for decades in the animal reservoir.

Notably, the data also provide evidence that the outbreak resulted from a single zoonotic transmission event with limited human-to-human transmission, rather than multiple independent zoonotic transmission events. The Rwandan MVD outbreak prompted a thorough investigation that included contact tracing, clinical assessment, travel history, sequencing, and serology testing, to trace the virus’s origin. Results of investigations linked the index case to a mining cave inhabited byRousettus aegyptiacus(the Egyptian fruit bat), where three individuals tested seropositive for IgG and IgM, further supporting the zoonotic origin of the outbreak through human-animal interactions.
Zero-shot extraction of seizure outcomes from clinical notes using generative pretrained transformers
Authors: Ojemann William K.S. , Xie Kevin , Liu Kevin , Chang Ellie , Roth Dan , Litt Brian , Ellis Colin A.
Published: November 2024

Purpose

Pre-trained encoder transformer models have extracted information from unstructured clinic note text but require manual annotation for supervised fine-tuning. Large, Generative Pre- trained Transformers (GPTs) may streamline this process. In this study, we explore GPTs in zero- and few-shot learning scenarios to analyze clinical health records.

Materials and Methods

We prompt-engineered LLAMA2 13B to optimize performance in extracting seizure freedom from epilepsy clinic notes and compared it against zero-shot and fine-tuned Bio+ClinicalBERT models. Our evaluation encompasses different prompting paradigms, including one-word answers, elaboration-based responses, prompts with date formatting instructions, and prompts with dates in context.

Results

We found promising median accuracy rates in seizure freedom classification for zero-shot GPT models: one-word – 62%, elaboration – 50%, prompts with formatted dates – 62%, and prompts with dates in context – 74%. These outperform the zero-shot Clinical BERT model (25%) but fall short of the fully fine-tuned BERT model (84%). Furthermore, in sparse contexts, such as notes from general neurologists, the best performing GPT model (76%) surpasses the fine-tuned BERT model (67%) in extracting seizure freedom.

Conclusion

This study demonstrates the potential of GPTs in extracting clinically relevant information from unstructured EMR text, offering insights into population trends in seizure management, drug effects, risk factors, and healthcare disparities. Moreover, GPTs exhibit superiority over task-specific models in contexts with the potential to include less precise descriptions of epilepsy and seizures, highlighting their versatility. Additionally, simple prompt engineering techniques enhance model accuracy, presenting a framework for leveraging EMR data with zero clinical annotation.

Competing Interests

The authors declare no financial or non-financial competing interests.
Single-Nucleus Atlas of Cell-Type Specific Genetic Regulation in the Human Brain
Authors: Zeng Biao , Yang Hui , Prashant N.M. , Venkatesh Sanan , Mathur Deepika , Auluck Pavan , Bennett David A. , Marenco Stefano , Haroutunian Vahram ,   PsychAD Consortium, Voloudakis Georgios , Lee Donghoon , Fullard John F. , Bendl Jaroslav , Girdhar Kiran , Hoffman Gabriel E. , Roussos Panos
Published: November 2024

Genetic risk variants for common diseases are predominantly located in non-coding regulatory regions and modulate gene expression. Although bulk tissue studies have elucidated shared mechanisms of regulatory and disease-associated genetics, the cellular specificity of these mechanisms remains largely unexplored. This study presents a comprehensive single-nucleus multi-ancestry atlas of genetic regulation of gene expression in the human prefrontal cortex, comprising 5.6 million nuclei from 1,384 donors of diverse ancestries. Through multi-resolution analyses spanning eight major cell classes and 27 subclasses, we identify genetic regulation for 14,258 genes, with 857 showing cell type-specific regulatory effects at the class level and 981 at the subclass level. Colocalization of genetic variants associated with gene regulation and disease traits uncovers novel cell type-specific genes implicated in Alzheimer’s disease, schizophrenia, and other disorders, which were not detectable in bulk tissue analyses. Analysis of dynamic genetic regulation at the single nucleus level identifies 2,073 genes with regulatory effects that vary across developmental trajectories, inferred from a broad age range of donors. We also uncover 1,655 genes withtrans-regulatory effects, revealing distal regulation of gene expression. This high-resolution atlas provides unprecedented insight into the cell type-specific regulatory architecture of the human brain, and offers novel mechanistic targets for understanding the genetic basis of neuropsychiatric and neurodegenerative diseases.
Enhancing retention on antiretroviral therapy at 6 months using interactive two-way texting: findings from a randomized controlled trial in Lilongwe, Malawi
Authors: Kiruthu-Kamamia Christine , Klabbers Robin E. , Tweya Hannock , Huwa Jacqueline , Thawani Agness , Bisani Pachawo , Chintedza Joseph , Chiwaya Geldert , Kudzala Aubrey G. , Ndhlovu Dumisani , Seyani Johnnie , Groot Wim , Pavlova Milena , Feldacker Caryl
Published: November 2024

Antiretroviral therapy (ART) retention is critical for achieving viral load suppression (VLS) among people living with HIV (PLHIV). Retention remains challenging in high-prevalence settings like Malawi. Short messaging service (SMS) interventions, particularly hybrid two-way texting (2wT), show promise in improving ART retention. We conducted a randomized control trial (RCT) at Lighthouse Trust in Lilongwe, Malawi, to evaluate the effectiveness of a hybrid 2wT system to improve early retention, appointment attendance, and VLS among new ART initiates within six months of ART initiation. After receiving routine ART initiation counseling, 452 new ART clients with mobile phones were randomized to 2wT or standard of care (SoC). The 2wT group received weekly motivational messages, appointment reminders, and had access to an open-ended SMS communication channel with healthcare workers. The SoC group received peer support at clinic visits and visit reminder phone calls. All participants were traced if they missed a clinic appointment by 14 days. Study outcomes included: retention in care (alive on ART), appointment adherence (attending within 2 days), and VLS (< 200 copies) at six months. Data from electronic medical records were analyzed using Chi-square tests and multivariable logistic regression. At six months post ART initiation, the 2wT group demonstrated significantly higher appointment adherence (59.6% vs. 46.8%, p = 0.008) and VLS (97.5% vs. 93.2%, p=0.007) compared to SoC. Among both 2wT and SoC, 91% remained in care (p=0.68). Although retention among 2wT and SoC at 6 months did not differ, 2wT clients were more likely to attend clinic visits on time and reach VLS in the first six months. The low-tech 2wT approach offers a scalable, appropriate intervention to enhance visit compliance and VLS among PLHIV with mobile phones. Implementing 2wT study over a longer time frame and among more clients would likely provide evidence for scaling 2wT more broadly.
Characterization of human senescent cell biomarkers for clinical trials
Authors: Farr Joshua N. , Monroe David G. , Atkinson Elizabeth J. , Froemming Mitchell N. , Ruan Ming , LeBrasseur Nathan K. , Khosla Sundeep
Published: November 2024

There is an increasing need for blood-based biomarkers of senescent cell burden to facilitate selection of participants for clinical trials. Potential candidates includep16Ink4aexpression in peripheral blood T-cells and circulating protein concentrations of the senescence-associated secretory phenotype (SASP).p16Ink4ais encoded by theCDKN2Alocus, which produces six variant transcripts in humans, two of which encode homologous p16 proteins: p16Inka4a, encoded byp16_variant 1, and p16Ɣ, encoded byp16_variant 5. While distinct quantitative polymerase chain reaction primers can be designed forp16_variant 5, primers forp16_variant 1also measurep16_variant 5(p16_variant 1+5). In a recent clinical trial evaluating effects of the senolytic combination, dasatinib + quercetin (D+Q), on bone metabolism in postmenopausal women, we found that women in the highest tertile for T-cell expression ofp16_variant 5had the most robust skeletal responses to D+Q. Importantly, assessment ofp16_variant 5was more predictive of these responses thanp16_variant 1+5. Here, we provide a comprehensivein vitroandin vivocharacterization ofp16_variant 5expression.In vitro, p16_variant 1increased rapidly (week 1) following the induction of DNA damage, whereasp16_variant 5increased later (week 4), consistent with the latter being more specific for an established senescent state. Further analysis of our clinical trial data identified a SASP panel in plasma that correlated withp16_variant 5expression in T-cells and performed as well in identifying postmenopausal women with a positive skeletal response to D+Q. Collectively, our findings support that the assessment of T-cellp16_variant 5expression may be more specific for senescence and provide further support for this assay as a biomarker for selecting participants in clinical trials of senolytic interventions. In addition, our data indicate that correlated plasma SASP markers could be used in lieu of the more technically challenging T-cellp16assay. Finally, the ability to identify individuals with a beneficial skeletal response to D+Q using two different measures of senescent cell burden (i.e., the T-cellp16assay and the SASP score) provides further support for the hypothesis that the underlying senescent cell burden dictates the clinical response to a senolytic intervention.