bluuebunny/crossref_metadata_2025 huggingface dataset:
Reconstructing the Genetic Relationship between Ancient and Present-Day Siberian Populations
Authors: Gill Haechan , Lee Juhyeon , Jeong Choongwon
Published: March 2024

Human populations across a vast area in northern Eurasia, from Fennoscandia to Chukotka, share a distinct genetic component often referred to as the Siberian ancestry. Most enriched in present-day Samoyedic-speaking populations such as Nganasans, its origins and history still remain elusive despite the growing list of ancient and present-day genomes from Siberia. Here, we reanalyze published ancient and present-day Siberian genomes focusing on the Baikal and Yakutia, resolving key questions regarding their genetic history. First, we show a long-term presence of a unique genetic profile in southern Siberia, up to 6,000 yr ago, which distinctly shares a deep ancestral connection with Native Americans. Second, we provide plausible historical models tracing genetic changes in West Baikal and Yakutia in fine resolution. Third, the Middle Neolithic individual from Yakutia, belonging to the Belkachi culture, serves as the best source so far available for the spread of the Siberian ancestry into Fennoscandia and Greenland. These findings shed light on the genetic legacy of the Siberian ancestry and provide insights into the complex interplay between different populations in northern Eurasia throughout history.
Associations Between Onset Age of Orthostatic Hypotension and Incident Myocardial Infarction, Stroke, and Dementia: A Prospective Cohort Study
Authors: Liang Jie , Zhang Wenya , Pan Yang , Gao Darui , Wang Yongqian , Xie Wuxiang , Zheng Fanfan
Published: March 2024

Background

The associations of age at orthostatic hypotension onset with incident myocardial infarction (MI), stroke, and dementia remain unknown. This study aimed to examine whether younger onset age of orthostatic hypotension was associated with higher risks of incident MI, stroke, and dementia.

Methods

Data were obtained from the UK Biobank. Information on the diagnosis of orthostatic hypotension, MI, stroke, and dementia was collected at baseline (2006–2010) and follow-ups (median = 13 years). The propensity score matching method and the Cox proportional hazard models were employed.

Results

A total of 448 374 adults (mean age: 56.8 ± 8.1 years), of whom 3 795 had orthostatic hypotension, were included. orthostatic hypotension patients exhibited higher risks of developing MI, stroke, and dementia than non-orthostatic hypotension participants. Importantly, among orthostatic hypotension patients, younger onset age (per 10-year decrement) was significantly associated with high risks of MI (HR = 3.15, 95% CI: 2.54–3.90, p < .001), stroke (HR = 1.72, 95% CI: 1.33–2.23, p < .001), and dementia (HR = 1.26, 95% CI: 1.02–1.57, p = .034). After propensity score matching, orthostatic hypotension patients had significantly higher risks of MI, stroke, and dementia than matched controls among all onset age groups, and the HRs gradually increased with descending onset age.

Conclusions

Younger onset age of orthostatic hypotension was associated with higher risks of incident MI, stroke, and dementia, underscoring the necessity to pay additional attention to the cardiovascular health and neurocognitive status of individuals diagnosed with orthostatic hypotension at younger ages to attenuate subsequent risks of incident cardiovascular diseases and dementia.
Affinity targeting of therapeutic proteins to the bone surface—local delivery of sclerostin–neutralizing antibody enhances efficacy
Authors: Zhang Boya , Swanson William Benton , Durdan Margaret , Livingston Heather N , Dodd Michaela , Vidanapathirana Sachith M , Desai Alec , Douglas Lindsey , Mishina Yuji , Weivoda Megan , Greineder Colin F
Published: March 2024

Currently available biotherapeutics for the treatment of osteoporosis lack explicit mechanisms for bone localization, potentially limiting efficacy and inducing off-target toxicities. While various strategies have been explored for targeting the bone surface, critical aspects remain poorly understood, including the optimal affinity ligand, the role of binding avidity and circulation time, and, most importantly, whether or not this strategy can enhance the functional activity of clinically relevant protein therapeutics. To investigate, we generated fluorescent proteins (eg, mCherry) with site-specifically attached small molecule (bisphosphonate) or peptide (deca-aspartate, D10) affinity ligands. While both affinity ligands successfully anchored fluorescent protein to the bone surface, quantitative radiotracing revealed only modest femoral and vertebral accumulation and suggested a need for enhanced circulation time. To achieve this, we fused mCherry to the Fc fragment of human IgG1 and attached D10 peptides to each C-terminus. The mCherry-Fc-D10 demonstrated an ~80-fold increase in plasma exposure and marked increases in femoral and vertebral accumulation (13.6% ± 1.4% and 11.4% ± 1.3% of the injected dose/g [%ID/g] at 24 h, respectively). To determine if bone surface targeting could enhance the efficacy of a clinically relevant therapeutic, we generated a bone-targeted sclerostin-neutralizing antibody, anti-sclerostin-D10. The targeted antibody demonstrated marked increases in bone accumulation and retention (20.9 ± 2.5% and 19.5 ± 2.5% ID/g in femur and vertebrae at 7 days) and enhanced effects in a murine model of ovariectomy-induced bone loss (bone volume/total volume, connectivity density, and structure model index all increased [P < .001] vs untargeted anti-sclerostin). Collectively, our results indicate the importance of both bone affinity and circulation time in achieving robust targeting of therapeutic proteins to the bone surface and suggest that this approach may enable lower doses and/or longer dosing intervals without reduction in biotherapeutic efficacy. Future studies will be needed to determine the translational potential of this strategy and its potential impact on off-site toxicities.
Supplementing a Paper Questionnaire with Web and Two-Way Short Message Service (SMS) Surveys
Authors: Spiegelman Maura , Zotti Allison , Merlin Julia
Published: March 2024

When deciding which modes to offer, researchers consider cost, known respondent contact information, and potential mode effects. For a short survey on employment, we evaluate the effect of adding one of two new electronic data collection modes to a mailed questionnaire. We sent a survey to principals who previously responded to the National Center for Education Statistics’ (NCES) National Teacher and Principal Survey (NTPS) asking about their current job status. This questionnaire, known as the Principal Follow-up Survey (PFS), has typically been administered as a short paper form that is mailed to NTPS respondents. In 2022, the PFS introduced two new modes of completion, and principals were randomly assigned to receive: (i) a paper form only; (ii) a paper form, as well as emails with a direct link to complete a web survey; or (iii) a paper form, as well as invitations by text message to complete an automated two-way short message service text survey by responding to texted “yes/no” questions. This article compares overall response rates and time-to-response by mode to determine respondent preferences for completing short surveys. Adding either electronic mode significantly increased response rates and decreased the number of days in which completed surveys were received, compared to offering only a paper questionnaire. Although email and text messages are both forms of electronic communication that may be accessible on a smartphone, the added text message survey resulted in higher response rates than the added web survey. This suggests that respondents interact differently with emails and text messages they receive and that offering an option to complete a survey by text message can increase the speed and efficiency of data collection for short surveys.
Shaping leaves through TALE homeodomain transcription factors
Authors: Byrne Mary E , Imlay Eleanor , Ridza Nazuratul Nabilah Binti
Published: March 2024

The first TALE homeodomain transcription factor gene to be described in plants was maize knotted1 (kn1). Dominant mutations in kn1 disrupt leaf development, with abnormal knots of tissue forming in the leaf blade. kn1 was found to be expressed in the shoot meristem but not in a peripheral region that gives rise to leaves. Furthermore, KN1 and closely related proteins were excluded from initiating and developing leaves. These findings were a prelude to a large body of work wherein TALE homeodomain proteins have been identified as vital regulators of meristem homeostasis and organ development in plants. KN1 homologues are widely represented across land plant taxa. Thus, studying the regulation and mechanistic action of this gene class has allowed investigations into the evolution of diverse plant morphologies. This review will focus on the function of TALE homeodomain transcription factors in leaf development in eudicots. Here, we discuss how TALE homeodomain proteins contribute to a spectrum of leaf forms, from the simple leaves of Arabidopsis thaliana to the compound leaves of Cardamine hirsuta and species beyond the Brassicaceae.
Recent advances in UV-B signalling: interaction of proteins with the UVR8 photoreceptor
Authors: Liu Wei , Jenkins Gareth I
Published: March 2024

The UV RESISTANCE LOCUS 8 (UVR8) photoreceptor mediates many plant responses to UV-B and short wavelength UV-A light. UVR8 functions through interactions with other proteins which lead to extensive changes in gene expression. Interactions with particular proteins determine the nature of the response to UV-B. It is therefore important to understand the molecular basis of these interactions: how are different proteins able to bind to UVR8 and how is differential binding regulated? This concise review highlights recent developments in addressing these questions. Key advances are discussed with regard to: identification of proteins that interact with UVR8; the mechanism of UVR8 accumulation in the nucleus; the photoactivation of UVR8 monomer; the structural basis of interaction between UVR8 and CONSTITUTIVELY PHOTOMORPHOGENIC 1 (COP1) and REPRESSOR OF UV-B PHOTOMORPHOGENESIS (RUP) proteins; and the role of UVR8 phosphorylation in modulating interactions and responses to UV-B. Nevertheless, much remains to be understood, and the need to extend future research to the growing list of interactors is emphasized.
Beyond content: discriminatory power of function words in text type classification
Authors: Venglařová Klára , Matlach Vladimír
Published: March 2024

Our work aims to evaluate the strength of the association between function words and several text types: novels, poems, academic articles, reviews, and blog posts, and the accuracy of their classification to these categories, through machine-learning and statistical methods. The principal conclusion is that the types of texts are distinguishable based only on the function words, either by vocabulary or vocabulary diversity. Such findings may impact the techniques of authorship attribution based on function words and text clustering techniques since some function words add information about the text types/genres, in addition to content words.
Data Management in Multicountry Consortium Studies: The Enterics For Global Health (EFGH) Shigella Surveillance Study Example
Authors: Feutz Erika , Biswas Prasanta K , Ndeketa Latif , Ogwel Billy , Onwuchekwa Uma , Sarwar Golam , Sultana Shazia , Peñataro Yori Pablo , Acebedo Alyssa , Ahmed Naveed , Ahmed Imran , Atlas Hannah E , Awuor Alex O , Bhuiyan Md Amirul Islam , Conteh Bakary , Diawara Oualy , Elwood Sarah , Fane Moussa , Hossen Md Ismail , Ireen Mahzabeen , Jallow Abdoulie F , Karim Mehrab , Kosek Margaret N , Kotloff Karen L , Lefu Clement , Liu Jie , Maguire Rebecca , Qamar Farah Naz , Ndalama Maureen , Ochieng John Benjamin , Okonji Caleb , Paredes Loyda Fiorella Zegarra , Pavlinac Patricia B , Perez Karin , Qureshi Sonia , Schiaffino Francesca , Traore Moussa , Tickell Kirkby D , Wachepa Richard , Witte Desiree , Cornick Jennifer , Jahangir Hossain M , Khanam Farhana , Olortegui Maribel Paredes , Omore Richard , Sow Samba O , Yousafzai Mohammad Tahir , Galagan Sean R
Published: March 2024

Background

Rigorous data management systems and planning are essential to successful research projects, especially for large, multicountry consortium studies involving partnerships across multiple institutions. Here we describe the development and implementation of data management systems and procedures for the Enterics For Global Health (EFGH) Shigella surveillance study—a 7-country diarrhea surveillance study that will conduct facility-based surveillance concurrent with population-based enumeration and a health care utilization survey to estimate the incidence of Shigella­-associated diarrhea in children 6 to 35 months old.

Methods

The goals of EFGH data management are to utilize the knowledge and experience of consortium members to collect high-quality data and ensure equity in access and decision-making. During the planning phase before study initiation, a working group of representatives from each EFGH country site, the coordination team, and other partners met regularly to develop the data management systems for the study.

Results

This resulted in the Data Management Plan, which included selecting REDCap and SurveyCTO as the primary database systems. Consequently, we laid out procedures for data processing and storage, study monitoring and reporting, data quality control and assurance activities, and data access. The data management system and associated real-time visualizations allow for rapid data cleaning activities and progress monitoring and will enable quicker time to analysis.

Conclusions

Experiences from this study will contribute toward enriching the sparse landscape of data management methods publications and serve as a case study for future studies seeking to collect and manage data consistently and rigorously while maintaining equitable access to and control of data.
Diarrhea Case Surveillance in the Enterics for Global Health Shigella Surveillance Study: Epidemiologic Methods
Authors: Atlas Hannah E , Conteh Bakary , Islam Md Taufiqul , Jere Khuzwayo C , Omore Richard , Sanogo Doh , Schiaffino Francesca , Yousafzai Mohammad Tahir , Ahmed Naveed , Awuor Alex O , Badji Henry , Cornick Jennifer , Feutz Erika , Galagan Sean R , Haidara Fadima C , Horne Bri’Anna , Hossen Md Ismail , Hotwani Aneeta , Houpt Eric R , Jallow Abdoulie F , Karim Mehrab , Keita Adama Mamby , Keita Youssouf , Khanam Farhana , Liu Jie , Malemia Thandizo , Manneh Alhagie , McGrath Christine J , Nasrin Dilruba , Ndalama Maureen , Ochieng John Benjamin , Ogwel Billy , Paredes Olortegui Maribel , Zegarra Paredes Loyda Fiorella , Pinedo Vasquez Tackeshy , Platts-Mills James A , Qudrat-E-Khuda Syed , Qureshi Sonia , Hasan Rajib Md Nazmul , Rogawski McQuade Elizabeth T , Sultana Shazia , Tennant Sharon M , Tickell Kirkby D , Witte Desiree , Peñataro Yori Pablo , Cunliffe Nigel A , Hossain M Jahangir , Kosek Margaret N , Kotloff Karen L , Qadri Firdausi , Qamar Farah Naz , Tapia Milagritos D , Pavlinac Patricia B
Published: March 2024

Background

Shigella is a leading cause of acute watery diarrhea, dysentery, and diarrhea-attributed linear growth faltering, a precursor to stunting and lifelong morbidity. Several promising Shigella vaccines are in development and field efficacy trials will require a consortium of potential vaccine trial sites with up-to-date Shigella diarrhea incidence data.

Methods

The Enterics for Global Health (EFGH) Shigella surveillance study will employ facility-based enrollment of diarrhea cases aged 6–35 months with 3 months of follow-up to establish incidence rates and document clinical, anthropometric, and financial consequences of Shigella diarrhea at 7 country sites (Mali, Kenya, The Gambia, Malawi, Bangladesh, Pakistan, and Peru). Over a 24-month period between 2022 and 2024, the EFGH study aims to enroll 9800 children (1400 per country site) between 6 and 35 months of age who present to local health facilities with diarrhea. Shigella species (spp.) will be identified and serotyped from rectal swabs by conventional microbiologic methods and quantitative polymerase chain reaction. Shigella spp. isolates will undergo serotyping and antimicrobial susceptibility testing. Incorporating population and healthcare utilization estimates from contemporaneous household sampling in the catchment areas of enrollment facilities, we will estimate Shigella diarrhea incidence rates.

Conclusions

This multicountry surveillance network will provide key incidence data needed to design Shigella vaccine trials and strengthen readiness for potential trial implementation. Data collected in EFGH will inform policy makers about the relative importance of this vaccine-preventable disease, accelerating the time to vaccine availability and uptake among children in high-burden settings.
The Enterics for Global Health (EFGH) Shigella Surveillance Study in Mali
Authors: Keita Adama Mamby , Doh Sanogo , Juma Jane , Nasrin Dilruba , Traoré Awa , Onwuchekwa Uma , Maguire Rebecca , Haidara Fadima C , Sow Samba O , Kotloff Karen L , Tapia Milagritos D
Published: March 2024

Background

In 2002, the Centre pour le Développement des Vaccins du Mali (CVD-Mali) was established as a partnership between the Mali Ministry of Health and the University of Maryland, Baltimore. Since its creation, CVD-Mali has been dedicated to describing the epidemiology of infectious diseases, supporting the development of vaccines, and training a team of local researchers. CVD-Mali participated in the Global Enteric Multicenter Study from 2007 to 2010 and the Vaccine Impact on Diarrhea in Africa study from 2015 to 2018, where the importance of Shigella as an enteric pathogen was established.

Methods

In the Enterics for Global Health (EFGH) Shigella surveillance study, CVD-Mali will conduct Shigella surveillance at 4 health centers serving the population currently participating in a demographic surveillance system and will measure the local incidence of Shigella diarrhea and related outcomes in 6- to 35-month-old children. Antibiotic sensitivity patterns and the costs related to these cases will also be measured.

Results

We anticipate reporting the number of diarrhea episodes that are positive by stool culture, the antibiotic susceptibility of these isolates, and the management and outcomes of these cases.

Conclusions

In Mali, the EFGH study will contribute valuable information to understanding the burden of Shigella in this population. These data will inform the evaluation of vaccine candidates.
Epstein-Barr Virus DNA Is Associated With Conjunctival Squamous Cell Carcinomas: A Case-Control Study From Zimbabwe
Authors: Dube Mandishora Racheal S , Galati Luisa , Reich Richard R , Combes Jean-Damien , McKay-Chopin Sandrine , Makunike-Mutasa Rudo , Masanganise Rangarirai , Gwambiwa Bevele , Magombei Tricia , Zito Francesco Alfredo , Lagiou Pagona , Clifford Gary M , Giuliano Anna R , Coghill Anna E , Tommasino Massimo , Gheit Tarik
Published: March 2024

Incidence of conjunctival squamous cell carcinoma (cSCC) in Zimbabwe is >30-fold higher than the global average. cSCC risk is notably higher among people with human immunodeficiency virus, implicating impaired immune response and a yet unknown infectious etiology. Formalin-fixed, paraffin-embedded blocks from Zimbabwe, comprising conjunctival precancer (n = 78), invasive cSCC cases (n = 148) and nonmalignant eye lesions (n = 119), were tested for multiple DNA viruses using Luminex bead–based technology. Epstein-Barr virus (EBV) type 1 positivity was strongly associated with cSCC diagnosis (adjusted odds ratio [aOR], 5.6 [95% confidence interval {CI}, 3.0–10.4) and marginally associated with precancer (aOR, 2.1 [95% CI, 1.0–4.5]). On analyzing EBV transcriptional activity with any of LMP1, EBNA1, and BZLF1, RNA transcripts were detected in 5 of 112 controls, 3 of 67 precancers, and 10 of 139 cases and none were associated with conjunctival case status. Our EBV DNA data suggest that EBV may play a role in cSCC. However, the low detection rate of EBV RNA supports further investigation to infer causality.
Isotretinoin-induced myositis
Authors: Hague Oliver , Thanopoulou Vasiliki , Mangat Pamela , Singh Animesh , Stratton Richard , Malley Tamir
Published: March 2024

Retinoid-induced myositis is a phenomenon recognised in multiple case reports. We report a case of isotretinoin-induced myositis in an 18-year-old male patient. This case adds to the published literature as it demonstrates (i) myositis may occur after extended periods of isotretinoin use, (ii) should be considered as a differential diagnosis even when presenting asymmetrically and (iii) can continue to progress clinically and biochemically initially following the suspension of isotretinoin before being effectively treated with corticosteroids.
Closure of TB pulmonary cavern using endobronchial valve placement
Authors: Mskhaladze Teona , Tchkonia David , Vacharadze Kakha , Kiria Nana , Chkonia Mikolay
Published: March 2024

Introduction: Enhancing the efficacy of treatment for Multi-Drug Resistant (MDR) and Extensively Drug Resistant (XDR) Tuberculosis has prompted exploration into adjunctive therapies, such as Endobronchial Valve Placement (EVP) in addition to pharmacological interventions. Materials and Methods: EVP was performed utilizing a combination of rigid and flexible bronchoscopes to address airway hemorrhage and facilitate closure of TB cavities. The procedure involved the deployment of large valves (12 mm and 17 mm), necessitating the utilization of a rigid bronchoscope. Results: Sputum conversion was confirmed through culture analysis after one month, and chest CT scans revealed complete closure of the tuberculous cavity five months post the EVP procedure. Conclusion: We posit that when used in conjunction with anti-TB chemotherapy, this method holds promise for shortening treatment duration and improving overall efficacy.
Host–microbiome associations in saliva predict COVID-19 severity
Authors: Alqedari Hend , Altabtbaei Khaled , Espinoza Josh L , Bin-Hasan Saadoun , Alghounaim Mohammad , Alawady Abdullah , Altabtabae Abdullah , AlJamaan Sarah , Devarajan Sriraman , AlShammari Tahreer , Ben Eid Mohammed , Matsuoka Michele , Jang Hyesun , Dupont Christopher L , Freire Marcelo
Published: March 2024

Established evidence indicates that oral microbiota plays a crucial role in modulating host immune responses to viral infection. Following severe acute respiratory syndrome coronavirus 2, there are coordinated microbiome and inflammatory responses within the mucosal and systemic compartments that are unknown. The specific roles the oral microbiota and inflammatory cytokines play in the pathogenesis of coronavirus disease 2019 (COVID-19) are yet to be explored. Here, we evaluated the relationships between the salivary microbiome and host parameters in different groups of COVID-19 severity based on their oxygen requirement. Saliva and blood samples (n = 80) were collected from COVID-19 and from noninfected individuals. We characterized the oral microbiomes using 16S ribosomal RNA gene sequencing and evaluated saliva and serum cytokines and chemokines using multiplex analysis. Alpha diversity of the salivary microbial community was negatively associated with COVID-19 severity, while diversity increased with health. Integrated cytokine evaluations of saliva and serum showed that the oral host response was distinct from the systemic response. The hierarchical classification of COVID-19 status and respiratory severity using multiple modalities separately (i.e. microbiome, salivary cytokines, and systemic cytokines) and simultaneously (i.e. multimodal perturbation analyses) revealed that the microbiome perturbation analysis was the most informative for predicting COVID-19 status and severity, followed by the multimodal. Our findings suggest that oral microbiome and salivary cytokines may be predictive of COVID-19 status and severity, whereas atypical local mucosal immune suppression and systemic hyperinflammation provide new cues to understand the pathogenesis in immunologically compromised populations.
Influence of BOVAMINE DEFEND Plus on growth performance, carcass characteristics, estimated dry matter digestibility, rumen fermentation characteristics, and immune function in finishing beef steers
Authors: Miller Alexandra C , Mezzomo Rafael , Gomes Daiany I , Loh Huey Yi , Levenson Jonah R , Guimaraes Octavio , Tangredi Briana V , Zuchegno Sophie M , Chek Erlene , Cappellozza Bruno I , Schutz Jennifer S , Engle Terry E
Published: March 2024

One hundred and eighty crossbred beef steers (406.0 ± 2.2 kg) were used to determine the impact of a novel direct-fed microbial (DFM) on growth performance, carcass characteristics, rumen fermentation characteristics, and immune response in finishing beef cattle. Steers were blocked by body weight (BW) and randomly assigned, within block, to 1 of 2 treatments (3 replicates/treatment: 30 steers/replicate). Treatments included: (1) no DFM (control) and (2) DFM supplementation at 50 mg ∙ animal−1 ∙ d−1 (BOVAMINE DEFEND Plus). All steers were fed a high-concentrate finishing diet and individual feed intake was recorded daily via the GrowSafe system. BWs were collected every 28 d. On day 55, 10 steers per pen were injected with ovalbumin (OVA). Jugular blood samples were collected from each steer on days 0, 7, 14, and 21 post injection. On day 112, the same steers were injected again with OVA and intramuscularly with a pig red blood cell solution. Jugular blood samples were collected from each steer on days 0, 7, 14, and 21 post injection. On day 124, rumen fluid was collected from 3 steers per treatment and used to estimate in vitro rumen fermentation characteristics. Equal numbers of steers per treatment were transported to a commercial abattoir on days 145, 167, and 185 of the experiment, harvested, and carcass data were collected. Initial BW was similar across treatments. On days 28 and 55, steers receiving DFM had heavier BW (P < 0.01) compared to controls. The average daily gain was greater in DFM-supplemented steers from days 0 to 28 (P < 0.01) and days 0 to 55 (P < 0.01) of the experiment compared to controls. Overall dry matter intake (DMI) was greater (P < 0.04) and overall feed efficiency was similar in DFM-supplemented steers compared to controls. Dressing percentage (P < 0.02) was greater in steers receiving DFM compared to controls. Antibody titers to injected antigens were similar across treatments. However, red blood cell superoxide dismutase activity was greater (P < 0.05) in DFM-supplemented steers compared to controls. In vitro molar proportions of isobutyric and butyric acid were greater (P < 0.01) and dry matter (DM) digestibility tended (P < 0.07) to be greater in rumen fluid obtained from steers supplemented with DFM. These data suggest that BOVAMINE DEFEND Plus supplementation improves growth performance during the initial period of the finishing phase, increases overall DMI and dressing percentage, and may impact antioxidant status in beef cattle.
The metabolic fingerprint of Scots pine—root and needle metabolites show different patterns in dying trees
Authors: Hunziker Stefan , Nazarova Tatiana , Kather Michel , Hartmann Martin , Brunner Ivano , Schaub Marcus , Rigling Andreas , Hug Christian , Schönbeck Leonie , Bose Arun K , Kammerer Bernd , Gessler Arthur
Published: March 2024

The loss of leaves and needles in tree crowns and tree mortality are increasing worldwide, mostly as a result of more frequent and severe drought stress. Scots pine (Pinus sylvestris L.) is a tree species that is strongly affected by these developments in many regions of Europe and Asia. So far, changes in metabolic pathways and metabolite profiles in needles and roots on the trajectory toward mortality are unknown, although they could contribute to a better understanding of the mortality mechanisms. Therefore, we linked long-term observations of canopy defoliation and tree mortality with the characterization of the primary metabolite profile in needles and fine roots of Scots pines from a forest site in the Swiss Rhone valley. Our results show that Scots pines are able to maintain metabolic homeostasis in needles over a wide range of canopy defoliation levels. However, there is a metabolic tipping point at around 80–85% needle loss. Above this threshold, many stress-related metabolites (particularly osmoprotectants, defense compounds and antioxidants) increase in the needles, whereas they decrease in the fine roots. If this defoliation tipping point is exceeded, the trees are very likely to die within a few years. The different patterns between needles and roots indicate that mainly belowground carbon starvation impairs key functions for tree survival and suggest that this is an important factor explaining the increasing mortality of Scots pines.
Is the Child Opportunity Index a Factor in Surgical Outcomes for Adolescent Idiopathic Scoliosis?
Authors: Linden Gabriel S. , Lee Sydney , Cook Danielle , Birch Craig M. , Hedequist Daniel J. , Hresko M. Timothy , Hogue Grant D.
Published: March 2024

Background:

Low socioeconomic status (SES) has been previously associated with delays in orthopaedic care. However, it is unclear how SES impacts patients with adolescent idiopathic scoliosis (AIS), particularly regarding preoperative major coronal curve angle or surgical outcomes. Utilizing the Child Opportunity Index (COI)—an address-driven measure of pediatric education, health/environment, and SES—we investigated whether COI is associated with differences in preoperative scoliosis magnitude, age at surgery, and AIS surgical outcomes.

Methods:

Consecutive patients with AIS surgically treated at a single center from 2011 to 2017 were reviewed. COI was calculated by inserting a patient’s home address into the nationally available COI database to derive a COI value. COI is scored from 0.0 to 100.0 (0.0 is lowest, 100.0 is highest). Specifically, COI is categorized as very low (<20.0), low (20 to 39.9), moderate (40 to 59.9), high (60 to 79.9), and very high (≥80). Those without addresses were excluded. Patients without proper radiographs to assess curve correction were also excluded. A COI threshold of 60.0 was used to separate patients into a low (<60.0) or high COI (

) group based on published COI guidelines. Outcomes, including preoperative curve magnitude, age at surgery, percentage curve correction, operative time (OT), intraoperative estimated blood loss per level fused, length of stay, and complications, were compared across groups. Pearson correlation analysis was used to assess correlations between COI and preoperative curve magnitude, as well as age.

Results:

Four hundred four patients were included in the study, and 263 had 2-year follow-up data. Patients were an average age of 14.9 years old (range: 11.2 to 19.8), had a median COI of 76 (range: 4 to 100), and had a mean preoperative major curve angle of 59 degrees (range: 36 to 93). COI was significantly higher for white patients compared with non-white (80.0 vs 40.0, P< 0.001), and higher for non-Hispanic individuals (79.0 vs 15.0, P< 0.001). Patients with Low COI were associated with a lower OT per level fused (P= 0.003) and decreased postoperative complication risk (P= 0.02). COI was not associated with preoperative major coronal curve angle, age at surgery, or any other surgical outcomes.

Conclusion:

COI was significantly lower for non-white patients and those of Hispanic ethnicity. Patients from low COI backgrounds achieved similar surgical results as those from high COI addresses and had a decreased OT per level fused and complication incidence, though the clinical significance of these differences is unknown. Future prospective studies are needed to determine whether these findings are reproducible across other states and health systems.

Level of Evidence:

Level III—prognostic study.
HMOX1 regulates ferroptosis via mic14 and its impact on chemotherapy resistance in small-cell lung cancer
Authors: Sun Yujie , Zhang Jian
Published: March 2024

This study aimed to investigate the role and molecular mechanism of heme oxygenase-1 (HMOX1) in chemotherapy resistance in small-cell lung cancer (SCLC). Employed bioinformatics, qPCR, and Western Blot to assess HMOX1 levels in SCLC versus normal tissues and its prognostic relevance. CCK-8, flow cytometry, and thiobarbituric acid assays determined HMOX1’s impact on SCLC chemosensitivity, ferroptosis markers, lipid peroxidation, and mic14’s role in chemoresistance. In the GSE40275 and GSE60052 cohorts, HMOX1 expression was downregulated in SCLC tissues compared to normal tissues. Higher HMOX1 expression was associated with improved prognosis in the Sun Yat-sen University Cancer Hospital cohort and GSE60052 cohort. The RNA and protein levels of HMOX1 were reduced in drug-resistant SCLC cell lines compared to chemosensitive cell lines. Upregulation of HMOX1 increased chemosensitivity and reduced drug resistance in SCLC, while downregulation of HMOX1 decreased chemosensitivity and increased drug resistance. Upregulation of HMOX1 elevated the expression of ferroptosis-related proteins ACSL4, CD71, Transferrin, Ferritin Heavy Chain, and Ferritin Light Chain, while decreasing the expression of GPX4 and xCT. Conversely, downregulation of HMOX1 decreased the expression of ACSL4, CD71, Transferrin, Ferritin Heavy Chain, and Ferritin Light Chain, while increasing the expression of GPX4 and xCT. Upregulation of HMOX1 promoted cellular lipid peroxidation, whereas downregulation of HMOX1 inhibited cellular lipid peroxidation. Upregulation of HMOX1 reduced the RNA level of mic14, while downregulation of HMOX1 increased the RNA level of mic14. mic14 exhibited inhibitory effects on cellular lipid peroxidation in SCLC cells and contributed to reduced chemosensitivity and increased drug resistance in chemoresistant SCLC cell lines. HMOX1 plays a role in ferroptosis by regulating mic14 expression, thereby reversing chemoresistance in SCLC.
Bergaptol inhibits glioma cell proliferation and induces apoptosis via STAT3/Bcl-2 pathway
Authors: Huang Hao , Zhang Junrong , Wu Jianbing , Du Chunfu , Zheng Bo , Guo Zhangchao , Chen Ligang , Zhang Deming , Liu Luotong
Published: March 2024

Glioblastoma (GBM) is the most common primary malignant brain tumour and lacks therapeutic options with significant effects. The aberrant activation of STAT3 is a critical factor in glioma progression via activating multiple signalling pathways that promote glioma. Among them, the antiapoptotic gene Bcl-2 could be upregulated by p-STAT3, which is an important reason for the continuous proliferation of glioma. We previously reported that bergaptol, a natural furanocoumarin widely found in citrus products, exerts antineuroinflammatory effects by inhibiting the overactivation of STAT3. Here, we aimed to evaluate whether bergaptol could promote glioma apoptosis by inhibiting the STAT3/Bcl-2 pathway. This study found that bergaptol inhibited the proliferation and migration of GBM cell lines (U87 and A172) and promoted apoptosis in vitro. We also found that bergaptol significantly inhibited the STAT3/Bcl-2 pathway in GBM cells. U87 cells were implanted intracranially into nude mice to establish a glioma model, and glioma-bearing mice were treated with bergaptol (40 mg/kg). Bergaptol treatment significantly inhibited glioma growth and prolonged the glioma-bearing mice’s survival time. In addition, bergaptol administration also significantly inhibited the STAT3/Bcl-2 pathway of tumour tissue in vivo. Overall, we found that bergaptol could effectively play an antiglioma role by inhibiting STAT3/Bcl-2 pathway, suggesting the potential efficacy of bergaptol in treating glioma.
Pityriasiform drug eruption associated with venetoclax for acute myeloid leukaemia
Authors: Liu Timothy J. , McMeniman Erin K.
Published: March 2024

Venetoclax is a targeted antileukaemic therapy that has emerged as the primary treatment of acute myeloid leukaemia in patients of advanced age or who would otherwise be ineligible for standard chemotherapy. Despite the documented evidence of cutaneous side effects of venetoclax, few reports have clarified presenting cutaneous features beyond the descriptors ‘rash’ and ‘pruritus’. In this report, we describe the development of a pityriasiform drug eruption following venetoclax-based induction therapy for acute myeloid leukaemia. This study provides further evidence to characterise the range of cutaneous adverse events that are associated with venetoclax-based therapy. Further studies are needed to elucidate the epidemiology and pathophysiology of venetoclax-induced cutaneous toxicities.
The PUG Flap: Conjoined Profunda Artery Perforator and Upper Gracilis Flap for Breast Reconstruction
Authors: Abdulwadood Isra , Pflibsen Lacey R. , Jarvis Nicholas R. , Winocour Sebastian , Rebecca Alanna M. , Casey William J. , Reece Edward M.
Published: March 2024

Abdominal-based free flaps are the mainstay of autologous breast reconstruction; however, the region may not be ideal for patients with inadequate soft tissue or history of abdominal surgery. This case describes the use of a novel conjoined flap based on the profunda artery perforator and upper gracilis pedicles, named the perforator and upper gracilis (PUG) flap. This flap design aims to maximize medial thigh flap volume while ensuring robust tissue perforation. Here, we present our experience with the PUG flap in a breast cancer patient undergoing autologous reconstruction. The patient was a 41-year-old woman seeking nipple-sparing mastectomy and immediate autologous reconstruction with the PUG flap due to limited abdominal tissue availability. The gracilis and profunda artery perforator flaps were elevated using one boomerang-style skin paddle. Once harvested, the flaps were inset with antegrade and retrograde flow off the internal mammary arteries and both respective internal mammary veins. The donor site was closed in a V-Y pattern resulting in a thigh lift–type lift and concealed scar. In conclusion, the boomerang-style PUG flap maximizes medial thigh free tissue transfer volume, offers internal blood flow redundancy, and maintains good cosmesis of the donor site.
A Study on Geographic Correlation between Indoor Radon Exposure and Leukemia Incidence in Canada
Authors: Chen Jing
Published: March 2024

In Canada, leukemia is diagnosed at a rate of 15 cases per 100,000 persons and accounts for about 3% of all new primary cancers. In this study, geographical correlation between residential radon exposure and leukemia incidence was investigated at a provincial level with more accurate long-term radon measurement data in 21,330 homes and 10-y (2000–2009) age standardized incidence rates per 100,000 population for various subtypes of leukemia. The analyses showed that the incidence rate of non-Hodgkin lymphoma is statistically significantly correlated with average indoor radon (222Rn) concentration for Canadian females (p = 0.01210) but not for males. At a provincial level, the association between average indoor radon level and chronic lymphocytic leukemia incidence rate is statistically significant (p = 0.0167), and the correlation is somewhat stronger for females (p = 0.0043). No correlation was found between indoor radon exposure and any other subtypes of leukemia evaluated in this study.
Fusion-Flanged Intrascleral Intraocular Lens Fixation Technique: Simple, Safe, Efficient
Authors: Piyasoonthorn Pratan , Gacivut Puntanarach
Published: March 2024

Purpose:

To develop a new, sutureless intrascleral intraocular lens (IOL) fixation technique based on the Yamane double-needle and Canabrava 4-flanged techniques.

Methods:

The Fusion-Flanged technique involves using a 7-0 polypropylene suture loop threaded through the eyelets of the IOL. Afterward, both ends of the suture are passed outside the eye through a 27-gauge needle. This technique creates a single flange by joining the 2 suture ends through handheld cautery, and this flange is then embedded into the scleral tunnel to securely fix the IOL in place.

Results:

This technique was performed on a total of 7 aphakic patients. Four of them had encountered complications following manual small incision cataract surgery, while the remaining 3 experienced complications after phacoemulsification. The results indicated a significant improvement in visual acuity, with mean preoperative and postoperative corrected distance visual acuities of 0.77 ± 0.11 and 0.27 ± 0.08 (logarithm of the minimum angle of resolution [logMAR] units), respectively.

Conclusions:

The Fusion-Flanged intrascleral IOL fixation technique offers improvements in simplicity, safety, and the overall efficiency when compared to existing sutureless intrascleral fixation techniques. Notably, this technique is versatile and can be applied to both non-foldable and foldable IOLs.
Suboptimal visual outcome after femto-LASIK ablation in a high myopic patient
Authors: Nuijts Rudy M.M.A. , Ollivier Robin , Allan Bruce D. , Lawless Michael A. , Carones Francesco , Güell José Luis , Vinciguerra Paolo , Kohnen Thomas
Published: March 2024

A 28-year-old nurse had an aberration-free femto-laser in situ keratomileusis (LASIK) performed for her myopia of −6.25 −0.50 × 096 and −6.75 −0.50 × 175 in the right and left eye, respectively. Corrected distance visual acuity (CDVA) preoperatively was 20/16. Preoperatively, there were no abnormalities on Scheimpflug imaging, and a pachymetry of 585 μm was measured in both eyes. Flap thickness was 115 μm. The patient was quite nervous during the surgery.

Since the surgery, her uncorrected distance visual acuity (UDVA) and CDVA are suboptimal at 20/30 and 20/20 in the right eye, and 20/20 and 20/16 in the left eye. 3 months postoperatively, there is a stable manifest refraction of +0.25 −1.25 × 030 and +0.25 −0.00 × 0. The keratometric astigmatism in the Scheimpflug imaging is 1.2 diopter (D) × 114 and 0.4 D × 78 in the right and left eyes, respectively (FIgures 1 and 2). Thinnest pachymetry is 505 μm and 464 μm in the right and left eye, respectively. Her wavefront analysis shows refraction in a 6 mm zone of −0.99 −1.22 × 32 and −0.91 −0.36 × 136. The cycloplegic refraction is 1.25 −1.00 × 023 and +1.00 −0.25 × 006 (Figures 3 and 4).

What is the cause of the suboptimal visual outcome in this case? What would be your treatment strategy to improve visual outcome?
Association between plasma circulating tumor DNA and the prognosis of esophageal cancer patients: a meta-analysis
Authors: Zhang Haowen , Jin Tao , Peng Yuhao , Luan Siyuan , Li Xiaokun , Xiao Xin , Yuan Yong
Published: March 2024

Background:

The application of liquid biopsy analysis utilizing circulating tumor DNA (ctDNA) has gained prominence as a biomarker in specific cancer types. Nevertheless, the correlation between ctDNA and the prognostic outcomes of patients with esophageal cancer (EC) remains a subject of controversy. This meta-analysis aims to assess the correlation between ctDNA and the prognosis of EC patients.

Methods:

The authors systematically explored Embase, PubMed, and the Cochrane Database to identify studies reporting on the prognostic value of ctDNA in EC patients before November 2023. The primary outcome involved the determine of associations between ctDNA with overall survival (OS), disease-free survival (DFS)/recurrence-free survival (RFS), as well asprogression-free survival (PFS) among EC patients. Secondary outcomes encompassed a detailed subgroup analysis in the setting of EC, including parameters such as detection time, histological subtypes, treatment modalities, regions, anatomic locations, and detection methods. Publication bias was assessed utilizing Begg’s test, Egger’s test, and funnel plots. A sensitivity analysis was conducted by systematically excluding individual studies to evaluate the stability of the results.

Results:

A total of 1203 studies were initially screened, from which 13 studies underwent further analysis, encompassing 604 patients diagnosed with EC. The comprehensive pooled analysis indicated a significant association between the detection of ctDNA and poor OS (HR: 3.65; 95% CI: 1.97–6.75, P<0.001), DFS/RFS (HR: 6.08; 95% CI: 1.21–30.50, P<0.001), and PFS (HR: 2.84; 95% CI: 1.94–4.16, P<0.001). Subgroup analysis showed that ctDNA remained a consistent negative predictor of OS when stratified by different detection time, histological subtypes, regions, anatomic locations, and detection methods. Furthermore, subgroup analysis stratified by regions and study types demonstrated an association between ctDNA detection and poor PFS in EC patients.

Conclusion:

Our results indicate plasma ctDNA may serve as robust prognostic markers for OS, DFS/RFS, and PFS among EC patients. This finding suggests that plasma ctDNA could offer a highly effective approach for risk stratification and personalized medicine.
Outpatient surgery benchmarks and practice variation patterns: case controlled study
Authors: Zhang Chi , Shariq Omair , Bews Katherine , Poruk Katherine , Mrdutt Mary M. , Foster Trenton , Etzioni David A. , Habermann Elizabeth B. , Thiels Cornelius
Published: March 2024

Background:

Despite numerous potential benefits of outpatient surgery, there is currently a lack of national benchmarking data available for hospitals and surgeons to compare their own outcomes as they transition toward outpatient surgery.

Materials and methods:

Patients who underwent 14 common general surgery operations from 2016 to 2020 were identified in the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. Operations were selected based on frequency and the ability to be performed both inpatient and outpatient. Postoperative complications and readmissions were compared between patients who underwent inpatient vs outpatient surgery. After adjusting for patient comorbidities, multivariable models assessed the effect of patient characteristics on the odds of experiencing postoperative complications. A separate multi-institutional study of 21 affiliated hospitals assessed practice variation.

Results:

In 13 of the 14 studied procedures, complications were lower for patients who were selected for outpatient surgery (all P<0.01); minimally invasive (MIS) adrenalectomy showed no difference (P=0.61). Multivariable analysis confirmed these findings; the odds of experiencing any adverse events were lower following outpatient surgery in all operations but MIS adrenalectomy (OR 0.97; 95% CI: 0.47–2.02). Analysis of institutional practices demonstrated variation in the rate of outpatient surgery in certain breast, endocrine, and hernia repair operations.

Conclusions:

Institutional practice patterns may explain the national variation in the rate of outpatient surgery. While the present data does not support the adoption of outpatient surgery to less optimal candidates, addressing unexplained practice variations could result in improved utilization of outpatient surgery.