bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel Doppler Flowmetry Shaft for Postoperative Monitoring after Head and Neck Reconstructive Surgery
Authors: Onoda Satoshi , Satake Toshihiko , Katsuragi Ryohei , Kobayashi Kohta , Tsukura Kahori , Tachibana Gaku
Published: October 2023

Doppler flowmetry is one of the most popular methods of monitoring Doppler signals during reconstructive surgery of the body surface. However, because of the thick and straight structure of the shaft, it is difficult to perform in areas with limited space, such as the oral cavity. We used a new type of Doppler flowmetry shaft to postoperatively monitor the flap in the oral cavity. Compared with conventional Doppler flowmetry, the new type uses a thinner metal probe shaft that can easily be inserted in narrow and limited spaces, such as the oral cavity. Additionally, the tip of the metal probe is gently bent, thereby allowing the Doppler tip to be placed perpendicular to the surface of the skin flap. We used this new type of Doppler flowmetry shaft for 30 patients after head and neck reconstruction using free flap transfer because Doppler signals were difficult to hear using conventional Doppler flowmetry. For all 30 patients, the new Doppler flowmetry shaft was able to monitor free flaps. Vascular thrombosis or vascular spasm occurred in three patients; two patients had inadequate arterial flow caused by vasospasm and arterial thrombus, and one patient had a venous thrombus. These three patients required re-exploration, and all flaps survived. This new type of Doppler flowmetry is simple and noninvasive. Furthermore, it can easily be performed by nonphysician medical personnel, and is useful for monitoring patients after head and neck reconstructive surgery.
Vascularized Toe Proximal Interphalangeal Joint Transfer in Posttraumatic Fingers: Analysis of Prognostic Factors for Suboptimal Outcomes
Authors: Huang Chi-Wei , Lin Ming-Huei , Lee Che-Hsiung , Chen Shih-Heng , Hsu Chung-Cheng , Lin Cheng-Hung , Huang Ren-Wen , Lin Yu-Te
Published: October 2023

Background:

Posttraumatic finger osteoarthritis of the proximal interphalangeal joint (PIPJ) is a difficult problem. Over the past decade, we have reported several methods for improving the outcomes of vascularized toe joint transfer (VJT). In this study, we focused on determining poor prognostic factors which lead to a suboptimal outcome.

Methods:

A consecutive series of patients with posttraumatic osteoarthritis of the PIPJ who received VJT between January 2008 and January 2021 were enrolled in this study. The senior surgeon (Y.-T.L.) performed the surgery in all cases. In this retrospective study, we reexamine the initial trauma-related soft tissue and bony structure injuries of the recipient finger, to assess the baseline tissue quality before VJT. The injuries were classified into five major categories according to their anatomic region. The functional outcome parameters (including range of motion, percentage of use, and extensor lag of the transferred PIPJ) were collected. Univariate and multivariate linear regression analyses were performed using the generalized estimated equation model to identify the correlation between the injury category involved and functional outcome.

Results:

A total of 59 digits were enrolled. Our results revealed that the fingers with previous vascular injury that received revascularization procedures had relatively suboptimal functional outcomes. These fingers had a significantly lower percentage of use both before (β = −0.222, P = 0.006) and after (β = −0.177, P = 0.006) receiving secondary procedures to improve functional outcome.

Conclusions:

Patients with prior revascularization surgery were associated with a poor functional outcome after VJT.
Surgical or Nonsurgical Facial Rejuvenation: The Patients’ Choice
Authors: Corduff Niamh
Published: October 2023

Background:

Patients seeking a pan-facial rejuvenation may not receive appropriate medical advice on surgical versus nonsurgical treatments, resulting in those who are best-suited for surgery receiving nonsurgical options, and vice versa. Patients who requested total-face, nonsurgical revitalization were surveyed to understand the factors influencing this decision-making.

Methods:

Patients consulting for total facial rejuvenation were surveyed on their reasons for seeking nonsurgical versus surgical interventions by an investigator with 30 years of plastic surgery experience, practicing in a nonsurgical clinic alongside a dermatologist and aesthetic physician.

Results:

Of the 92 patients surveyed, 78% completed the survey, 47% of whom had considered facelift surgery, and 14% of whom proceeded to inquiries or consultations with a plastic surgeon about facelift surgery. All respondents were women, and age was not an exclusion factor. Forty-four percent would still consider facelifts in later life. Among the most common reasons for choosing nonsurgical approaches were a desire for natural and subtle results, cost, having flexibility in treatment choice, concerns about surgical and anesthesia risks, downtime, the ability to distribute treatments over time, and scarring.

Conclusions:

Many patients book nonsurgical treatments without prior professional advice, and consider these as a temporary solution, but may desire surgery later in life. Before conducting nonsurgical treatments, doctors should identify this group and avoid interventions that may interfere with optimal surgical outcomes later. Also, some patients desire surgical outcomes when surgery is not a feasible option, and thus seek nonsurgical alternatives. For this group, realistic goals must be set before treatment to avoid disappointment.
A Rare Case of Methotrexate-Associated Lymphoproliferative Disease in the Orbit
Authors: Spadaro Jane Z. , Perzia Brittany , Perincheri Sudhir , Habib Larissa
Published: October 2023

An 80-year-old Caucasian female with a history of rheumatoid arthritis presented with a 6-month history of progressive right upper eyelid ptosis, edema, erythema, and pain. MRI demonstrated a superior orbital mass. An incisional biopsy was performed, and pathologic analysis revealed an atypical lymphoid infiltrate, co-expressing both B and T-cell markers, with a low proliferation rate. Flow cytometry and IgH rearrangement study did not demonstrate any B- or T-cell monoclonal proliferation. Based on these findings, she was diagnosed with an iatrogenic immunodeficiency-associated lymphoproliferative disorder. Discontinuation of methotrexate resulted in the complete resolution of her symptoms, and she remains in remission 18 months later. Given the increased risk of lymphoproliferative disease in patients with rheumatoid arthritis, careful evaluation and close monitoring upon immunosuppressive medication withdrawal is necessary to confirm the diagnosis.
Long-term outcome of minimally invasive staging surgery for clinical stage I endometrial cancer: A single institute experience in Taiwan
Authors: Lu Ting-Fang , Lu Chien-Hsing , Sun Lou , Liu Chi-Ku , Shih Yu-Hsiang , Hwang Sheau-Feng , Hsu Shih-Tien
Published: October 2023

Background:

Endometrial cancer is the most common gynecological cancer in developed countries. With recent advances in equipment and knowledge, minimally invasive surgery (MIS) is widely accepted for the treatment of endometrial cancer. This study had the largest number of cases to date in Taiwan, comparing outcomes between MIS and laparotomy staging surgery using real-world data with long-term follow-up.

Methods:

We retrospectively reviewed patients with clinical stage 1 endometrial cancer from 2009 to 2020 in our institute. All patients underwent comprehensive surgical staging procedures by MIS or laparotomy. The safety, morbidity, progression-free survival (PFS), and overall survival (OS) rates of the two groups were compared. Clinical and pathologic factors were compared with Chi-square and Fisher Exact test. PFS and OS were estimated by the Kaplan-Meier method. Differences between survival curves were analyzed using the log-rank test. A p value of <0.05 was considered statistically significant. Using Cox proportional hazards models, all factors found to be significantly associated with risk of recurrence on univariate analyses were then assessed together through multivariable models, resulting in a final oncologic outcome between MIS and laparotomy.

Results:

A total of 665 cases (412 cases in MIS group and 253 cases in laparotomy group) were enrolled for data analysis. Median operation time was shorter in MIS group (244 and 265 minutes, p < 0.001). Median blood loss was also less (75 and 430 mL, p < 0.001). Median postoperative hospitalization duration was longer in the laparotomy group (2 and 7 days, p = 0.001). After adjusting presurgery risk factors, the PFS and OS were no significant difference in MIS and laparotomy groups.

Conclusion:

Using real-world data with long-term follow-up, we could confirm excellent PFS and OS in selective patients with clinical stage 1 endometrial carcinoma who received MIS, and the surgical time, hospital day, and blood loss were also less.
Physician Assistants/Associates With Doctoral Degrees: Where Are They Now?
Authors: Klein Alicia , Kayingo Gerald , Schrode Katrina M. , Soria Krista
Published: October 2023

Purpose

The impact of holding a doctoral credential by clinically practicing physician assistants/associates (PAs) remains unknown. The purpose of this study was to investigate practice patterns and describe demographic characteristics of PAs who have terminal doctoral degrees.

Methods

This was a secondary analysis of data obtained from the 2021 Salary Survey of the American Academy of PAs. A total of 13,865 PAs responded to the survey for an estimated response rate of 13.3%. We examined the relationships between holding a doctoral degree, demographic characteristics, and work-related variables. Descriptive bivariate statistics and chi-square tests were used for data analysis.

Results

Most of the PAs (93.6%) with doctoral degrees were older than 30 years and self-identified as female (55%). There were higher proportions of non-White individuals among those with doctorates compared with general PA population. Of the PAs holding doctoral degrees, 90.4% were primarily clinicians and 9.6% were primarily educators. Physician assistants/associates with doctoral degrees were employed with their current employer longer than PAs without doctoral degrees. Most of the PAs with doctoral degrees held informal or formal leadership and had an annual salary above the median (62.3%) compared with PAs without doctoral degrees (40.0%).

Conclusion

There are statistically significant differences in practice patterns and demographic factors between PAs with and without doctoral degrees. Physician assistants/associates with doctoral degrees were older, were male, and held leadership positions. Taken together, holding a doctoral credential may improve upward mobility at workplaces. Qualitative studies are warranted to further understand the motivation and impact of holding a doctoral credential among clinically practicing PAs.
Long-term outcome of a cohort of Italian patients affected with alpha-Mannosidosis
Authors: Bertolini Anna , Rigoldi Miriam , Cianflone Annalia , Mariani Raffaella , Piperno Alberto , Canonico Francesco , Cefalo Graziella , Carubbi Francesca , Simonati Alessandro , Urban Maria Letizia , Beccari Tommaso , Parini Rossella
Published: October 2023

Alpha-mannosidosis (MIM #248500) is an ultra-rare autosomal recessive lysosomal storage disease with multi-system involvement and a wide phenotypic spectrum. Information on long-term outcomes remains poor. We present the long-term outcomes (median, 19 years) of nine patients with alpha-mannosidosis, three females and six males, followed at a single center. The findings of the nine patients were collected from medical records and reported as mean ± SD or median, and range. The age of onset of the first symptoms ranged from 0–1 to 10 years. The diagnostic delay ranged from 2 to 22 years (median= 11 years). Coarse face, hearing, heart valves, joints, gait, language, dysarthria, psychiatric symptoms, I.Q., MRI, walking disabilities, orthopedic disturbances and surgeries showed a slow worsening over the decades. Our patients showed a slowly worsening progressive outcome over the decades. Psychiatric symptoms were present in 100% of our population and improved with the appropriate pharmacological intervention. This aspect requires attention when following up on these patients. Our description of the long-term evolution of alpha-mannosidosis patients may provide basic knowledge for understanding the effects of specific treatments.
Update on the genetic basis of obstructive sleep apnoea – hype or hope?
Authors: Riha Renata L.
Published: October 2023

Purpose of review

The obstructive sleep apnoea syndrome (OSAS) is a chronic, common condition in western societies which can lead to adverse cardiometabolic effects if left untreated and is one of the commonest causes of excessive daytime somnolence.

Recent findings

The presentation of OSAS is diverse and is thought to comprise of different intermediate phenotypes and endotypes in varying proportions in each individual. Unfortunately, due to its heterogeneity and the changing definitions of the disorder by workers in the field, attempts at revealing the genetic basis of OSAS has been fraught with difficulty.

This brief review presents a short update on the achievements of the past three decades in this understudied and underfunded area of endeavour in respiratory sleep medicine. The genetic underpinnings of OSAS remain elusive.
Prediction of the bacterial shape in urinary tract infections with the Sysmex UF-1000i analyser: technical note
Authors: Benhamza Noussaiba , Aarab Adnane , Farih Soumya , Saddari Abderrazak , Yacoubi Loubna , Benaissa Elmostapha , Ben Lahlou Yassine , Elouennass Mostafa , Maleb Adil
Published: October 2023

Background:

The aim of our study was to explore the utility of the Sysmex UF-1000i analyzer as a rapid screening tool for urinary tract infections (UTI) and its ability to predict bacterial shape in order to help physicians choose the appropriate empiric treatment.

Materials and methods:

This is a retrospective study, including 1023 urine cytobacteriological examinations. Urines were processed according to the recommendations of the medical microbiology reference system (REMIC). Using the Sysmex Uf-1000i analyzer, the authors evaluated bacteria forward scatter (B_FSC) and fluorescent light scatter (B_FLH) in a preliminary discrimination step for UTI caused by bacilli or cocci bacteria.

Results:

The authors got 1023 positive samples. Comparing baccili and cocci bacteria, the authors observed a statistically significant difference for B_FSC but not for B_FLH. The values of B_FLH are very close for the four categories of microorganisms compared (bacilli, cocci, bacilli–cocci association, and yeasts). For these same categories, tests show different values for the B_FSC. A separate analysis of the B_FSC values for bacilli shows that their distribution is relatively homogeneous and exhibits a peak between 20 and 30 ch.

Conclusion:

Dimensional parameters of bacteria generated by UF-1000i could be a rapid and useful tool for predicting the bacterial shape causing UTI.
Herpes simplex virus infection and the risk of dementia: a systematic review and meta-analysis
Authors: Elhalag Rowan H. , Motawea Karam R. , Talat Nesreen E. , Rouzan Samah S. , Mahmoud Nada , Hammad Elsayed M. , Reyad Sarraa M. , Mohamed Mai S. , Shah Jaffer
Published: October 2023

Aim:

The authors aimed to perform a meta-analysis to evaluate the association between herpes simplex virus (HSV) infection and the risk of developing dementia.

Methods:

The authors searched the following databases: PubMed, Scopus, Cochrane Library, and Web of Science. The authors included any randomized control trials and controlled observational studies that investigated the prevalence of dementia in HSV-infected patients and HSV-free control group. Also, if the studies measured the levels of HSV antibodies and incidence of these antibodies in patients with dementia compared with a healthy control group.

Results:

After a comprehensive literature search, 19 studies were included in the meta-analysis with 342 535 patients included in the analysis. The pooled analysis showed a statistically significant association between Alzheimer’s disease (AD), mild cognitive impairment (MCI), and increased levels of IgG titer group [mean difference (MD) = 0.99, 95% confidence interval (CI) = 0.36–1.63, P-value = 0.002], (MD = 0.80, 95% CI = 0.26–1.35, P-value = 0.004), respectively. Additionally, the generic inverse variance showed a statistically significant association between the HSV group and increased incidence of dementia compared with the no HSV control group [risk ratio (RR) = 2.23, 95% CI = 1.18–2.29, P-value <0.00001]. Moreover, this analysis showed no statistically significant difference between the AD group and the control group in anti-HSV IgM titer n (%) outcome (RR = 1.35, 95% CI = 0.91–2.01, P-value = 0.14), respectively.

Conclusion:

This study revealed that AD and MCI patients have increased levels of IgG antibodies titer against HSV infection. The study showed a significant association between HSV infection and increased incidence of dementia. Thus, regular follow-up of HSV patients’ IgG titer levels could be useful in the prevention of dementia in these patients.
Low-dose atorvastatin therapy induced rhabdomyolysis in a liver cirrhosis patient – a case report
Authors: Bhattarai Shashank , Pradhan Sandip R. , Bhattarai Shraddha
Published: October 2023

Introduction:

Rhabdomyolysis may arise due to traumatic or non-traumatic causes leading to muscle injury. However, increased statin use has raised drug-related side effects like statin-related muscle damage.

Case report:

A 74-year-old male with liver cirrhosis secondary to alcohol was prescribed atorvastatin for hyperlipidemia. He developed muscle tenderness and decreased muscle power 2 weeks following statin therapy, evident with a creatine phosphokinase level of more than 22 000 IU/l. The urinalysis also revealed positive for blood. Hence, atorvastatin was ceased. The patient’s laboratory parameters improved significantly, implying atorvastatin is the causative agent for rhabdomyolysis.

Discussion:

Statins are usually safe and well-tolerated drugs; however, skeletal muscle symptoms occur in ~5–10% of patients. The risk factor for statin-induced muscle injury includes advanced age, drug-altering statin plasma level, liver disease, or chronic kidney disease. Moreover, the hepatic level of CYP450 and its CYP3A4 isoform are altered in chronic liver diseases. CYP3A4 isoenzyme and its activity declines in hepatic cirrhosis patients.

Conclusion:

Statins are generally prescribed for hyperlipidemia and primary and secondary prevention in high-risk cardiovascular diseases. However, several risk factors alter statin metabolism, causing statin-induced muscle injury. Thus, despite several studies suggesting otherwise, special precautions should be taken in patients with chronic liver disease.
Lambda-cyhalothrin ingestion: an infrequent yet concerning presentation of pyrethroid poisoning
Authors: Silwal Prabhat , Adhikari Rojeena , Yadav Binay , Sah Sanjan K. , Bhatt Ajay , Basnet Samjhana
Published: October 2023

Introduction and importance:

Lambda-cyhalothrin is a type II pyrethroid compound commonly used as a pesticide, with the potential to cause life-threatening toxicity in humans. Furthermore, among cases of pesticide poisoning in Nepal, organophosphates are most frequently implicated.

Case presentation:

A 40-year-old female presented to our hospital after ingesting a pesticide compound with suicidal intent. She also admitted to alcohol intoxication and exhibited symptoms of confusion, abdominal pain, nausea, and vomiting. An atropine challenge test yielded negative results. Therefore, conservative management was continued. It was discovered later that the ingested pesticide was lambda-cyhalothrin. The patient’s condition eventually improved with supportive treatment.

Clinical discussion:

Several reports have highlighted the overlapping clinical features between organophosphorus and pyrethroid poisoning. In some cases of pyrethroid poisoning, misdiagnosis as organophosphorus poisoning has occurred, leading to the inappropriate administration of atropine. In our case, initial management was challenging owing to the lack of accurate information about the ingested compound. On further evaluation, cholinergic clinical features were absent and the atropine challenge test was negative. This was suggestive of nonorganophosphorus compound poisoning.

Conclusion:

This case illustrates that managing pesticide poisoning becomes challenging when the nature of the pesticide is unknown. Patients suffering from poisoning caused by pyrethroid compounds like lambda-cyhalothrin can present with features resembling organophosphorus poisoning. In such circumstances, a comprehensive clinical evaluation should guide the management. Clinical features and an atropine challenge test can aid in differentiating organophosphorus from nonorganophosphorus compound poisoning. This distinction facilitates therapeutic decision-making, including the consideration of atropine administration.
Pembrolizumab-Associated Pneumonitis Resembling Lymphangitic Carcinomatosis in a Melanoma Patient
Authors: Umehana Masaki , Hosono Makoto , Hijikata Yoichiro , Takahashi Mina , Kanagaki Mitsunori
Published: October 2023

In recent years, many articles have described the adverse events associated with immune checkpoint inhibitors. We report the case of a 63-year-old woman with bilateral lung shadows after 1-year pembrolizumab immunotherapy following surgery for the right-foot melanoma because of positive sentinel lymph nodes. Follow-up 18F-FDG PET/CT demonstrated bilateral diffuse mass-like peribronchovascular opacities with marked FDG uptake. Clinically, melanoma metastases with lymphangitic spread were suspected, and bronchoscopy was performed, although no evidence of malignancy was found. The lung shadow was mostly resolved after steroid treatment. Pembrolizumab-induced pneumonitis can be a mimicker of melanoma metastasis with lymphangitic spread.
Isolated Skull Metastasis With Unusual Spiculated Periosteal Reaction From Rectal Cancer Resembling Osteosarcoma on FDG PET/CT
Authors: Liu Mingyuan , Dong Aisheng , Zuo Changjin , Zhu Yan , Fu Xiaoling
Published: October 2023

We describe FDG PET/CT findings in a case of isolated skull metastasis with spiculated periosteal reaction from rectal mucinous adenocarcinoma 8 years after proctectomy. The skull metastasis showed heterogeneous FDG uptake and multiple short spicules of bone producing the sunburst appearance resembling primary osteosarcoma or Ewing sarcoma. Familiarity with this atypical imaging appearance of the bone metastasis from rectal cancer may be helpful for the diagnosis and differential diagnosis.
The Value of Transanal Normal Saline Infusion–Assisted Multipath Ultrasonography in the Diagnosis of T1/T2 Rectal Cancer
Authors: Wu Shengnan , Wei Linglin , Chen Hailan , Xu Yu , Zhou You , Liu Xinxiu
Published: October 2023

This study aims to assess the application value of transanal normal saline infusion–assisted multipath ultrasonography (TNSI-MU) in the diagnosis of T1/T2 rectal cancer (RC). All patients first received single-path 360-degree transrectal ultrasonography and then received 360-degree transrectal ultrasonography, transabdominal ultrasonography, or transvaginal ultrasonography after TNSI to determine the T stage. With surgical pathology as the criterion standard, the detection rates of T1/T2 RC lesions and the T-staging results of single-path 360-degree transrectal ultrasonography, TNSI-MU, and contrast-enhanced magnetic resonance imaging (MRI) were compared and analyzed. T1/T2 RC was surgically and pathologically confirmed in 52 patients. Single-path 360-degree transrectal ultrasonography had a lesion detection rate of 57.69% (30/52) and a T-staging accuracy of 80.0% (24/30), the sensitivity was 57.69%, and the specificity was 88.46%. Transanal normal saline infusion–assisted multipath ultrasonography had a lesion detection rate of 100%, and its T-staging accuracy was 84.62% (44/52), the sensitivity was 100%, and the specificity was 88.61%. Transanal normal saline infusion–assisted multipath ultrasonography had a significantly higher detection rate of T1/T2 RC lesions than single-path 360-degree transrectal ultrasonography (P < 0.001), but the 2 methods had similar T-staging accuracy for T1/T2 RC (χ2 = 0.286, P = 0.593). Contrast-enhanced MRI had a lesion detection rate of 100% and a T-staging accuracy of 40.38% (21/52), the sensitivity was 98.07%, and the specificity was 61.54%. Transanal normal saline infusion–assisted multipath ultrasonography had significantly higher diagnostic accuracy than contrast-enhanced MRI for T staging of T1/T2 RC (P < 0.001), and the diagnostic results of the 2 methods were not consistent (κ = 0.151). Transanal normal saline infusion–assisted multipath ultrasonography outperformed single-path 360-degree transrectal ultrasonography in the detection rate of T1/T2 RC lesions and contrast-enhanced MRI in the staging accuracy for T1/T2 RC.
Intercostal Nerve Cryoablation Reduces Opioid Use and Length of Stay Without Increasing Adverse Events
Authors: Linton Samuel C. , Tian Yao , Zeineddin Suhail , Alayleh Amin , De Boer Chris , Goldstein Seth D. , Ghomrawi Hassan M.K. , Abdullah Fizan
Published: October 2023

Objective:

To examine differences in opioid use, length of stay and adverse events after minimally invasive correction of pectus excavatum (MIRPE) with and without intercostal nerve cryoablation.

Summary Background Data:

Small studies show that intraoperative intercostal nerve cryoablation provides effective analgesia with no large-scale evaluations of this technique.

Methods:

The pediatric health information system database was used to perform a retrospective cohort study comparing patients undergoing MIRPE at children’s hospitals before and after initiation of cryoablation. The association of cryoablation use with inpatient opioid use was determined using quantile regression with robust standard errors. Difference in risk adjusted length of stay between the cohorts was estimated using negative binomial regression. Odds of adverse events between the two cohorts were compared using logistic regression with a generalized estimating equation.

Results:

5442 patients underwent MIRPE at 44 children’s hospitals between 2016 and 2022 with 1592 patients treated after cryoablation was introduced at their hospital. Cryoablation use was associated with a median decrease of 80.8 (95% CI: 68.6-93.0) total oral morphine equivalents as well as a decrease in estimated median length of stay from 3.5[3.2-3.9] days to 2.5[2.2-2.9] days (P-value 0.016). Cryoablation use was not significantly associated with an increase in any studied adverse events.

Conclusions:

Introduction of cryoablation for perioperative analgesia was associated with decreased inpatient opioid use and length of stay in a large sample with no change in adverse events. This novel modality for peri-operative analgesia offers a promising alternative to traditional pain management in thoracic surgery.
Propensity for selfing varies within a population of hermaphroditic snails: coexistence of selfers, outcrossers and mixed-mating individuals
Authors: Felmy Anja , Streiff Alena B. , Jokela Jukka
Published: October 2023

To understand mating-system evolution in self-compatible hermaphrodites, variation in selfing rates is highly relevant. Empirical studies are rarely designed to capture variation between individuals, instead often comparing species and populations. Yet, evolution primarily occurs within populations, rendering among-individual variation essential. Observed individual selfing rates depend on the environment (e.g. differences in mate availability) and individuals' propensity for selfing. We quantified individual variation in selfing propensity in the snail
Radix balthica
by conducting laboratory mating trials that manipulated mate availability (low versus moderate) and estimating selfing rates from progeny arrays. We also measured female lifetime fitness. We found substantial among-individual variation in selfing propensity, including pure selfers (32%), pure outcrossers (31%) and mixed-mating individuals that selfed and outcrossed (37%). Experimental levels of mate availability did not significantly affect selfing rates. Selfers had reduced female liftetime fitness. Our results show that the propensity for selfing can differ considerably among individuals, with similar proportions of selfers, outcrossers and mixed maters. As mate availability did not affect selfing, our ‘moderate’ experimental level of mate availability might still have been too low to prompt selfers to outcross. This and the observed fitness differences also cautiously suggest that investigating the heritability of selfing propensities might be worthwhile in this population.
Parallel worlds and mixed economies: multi-proxy analysis reveals complex subsistence systems at the dawn of early farming in the northeast Baltic
Authors: Oras Ester , Tõrv Mari , Johanson Kristiina , Rannamäe Eve , Poska Anneli , Lõugas Lembi , Lucquin Alexandre , Lundy Jasmine , Brown Samantha , Chen Shidong , Varul Liivi , Haferberga Vanda , Legzdiņa Dardega , Zariņa Gunita , Cramp Lucy , Heyd Volker , Reay Michaela , Pospieszny Łukasz , Robson Harry K. , Nordqvist Kerkko , Heron Carl , Craig Oliver E. , Kriiska Aivar
Published: October 2023

The transition from foraging to farming was a key turning point in ancient socio-economies. Yet, the complexities and regional variations of this transformation are still poorly understood. This multi-proxy study provides a new understanding of the introduction and spread of early farming, challenging the notions of hierarchical economies. The most extensive biological and biomolecular dietary overview, combining zooarchaeological, archaeobotanical, dietary stable isotope and pottery lipid residue analyses is presented, to unravel the nature and extent of early farming in the 3rd millennium cal BCE in the northeast Baltic. Farming was introduced by incoming Corded Ware cultural groups (CWC), but some dietary segregation existed within these communities, with some having more access to domesticates, others incorporating more wild resources into their diet. The CWC groups coexisted in parallel with local hunter–fisher–gatherers (HFG) without any indication of the adoption of domesticates. There was no transition from foraging to farming in the 3rd millennium cal BCE in the NE Baltic. Instead, we see a complex system of parallel worlds with local HFGs continuing forager lifeways, and incoming farmers practising mixed economies, with the continuation of these subsistence strategies for at least a millennium after the first encounter with domesticated animals.
Little bits of dragonfly history repeating exemplified by a new Pennsylvanian family
Authors: Yang Nan , Ren Dong , Béthoux Olivier
Published: October 2023

During its 320 Myr evolution, dragon- and damselfly (Odonata) wing morphology underwent intense modifications. The resulting diversity prompted comparative analyses focusing on phylogeny. However, homoplasy proved to plague wing-related characters. Concurrently, limited benefits were obtained from considering fossil taxa, similarly impacted. Herein, we investigate two aspects particularly affected by convergence, namely the acquisition of vein-like structuring elements derived from regular cross-venation, termed conamina; and the evolution of butter knife wing shape. Conamen implementation is found to be consistently linked with vein curvature sharpening, itself generating potential breaking points. Conamina therefore likely evolved to address wing integrity issues during ever-more-demanding flight performance. Moreover, an existing conamen is likely to trigger the acquisition of further, associated conamina. As for butter knife shape, previously documented in the extinct Archizygoptera and among damselflies, we report a new, 315 Ma occurrence with the rare speciesHaidilaozhen cuiaegen. et sp. nov. (family Haidilaozhenidae fam. nov.), from the Xiaheyan locality (China). The repeated acquisition of butter knife-shaped wing can be related to slow speed flight and, in turn, predator avoidance. In both cases of iterated regularities, the unique ‘network-and-membrane’ wing design proper to insects is found to compose a strong, constraining factor.
Developing a fast and catalyst-free protocol to form C=N double bond with high functional group tolerance
Authors: Zhong Bin , Chen Feng , Ge Yushu , Liu Dan
Published: October 2023

The carbon–nitrogen double bond (C=N) is a fundamentally important functional group in organic chemistry. This is largely due to the fact that C=N acts as electrophilic synthon to give nitrogen-containing compounds. Here, we report the condensation of primary amine or hydrazine with very electron-deficient aldehyde to form C=N bond in the absence of any catalysts (metals and acids). The protocol performs at room temperature and applies water as co-solvent. Two hundred examples are presented here. With its intrinsic advantages of wide substrate scopes, excellent efficiency (high yields and short reaction time), operational simplicity, mild condition (room temperature as reaction temperature, no catalysts, no additions, water as co-solvent and opening to air) and available starting materials, the protocol can be compatible with various drugs, prodrugs, dyes and pharmacophores containing primary amino group. In addition, we also successfully apply this protocol to rapidly synthesize the core scaffolds of bioactive molecules.
Characterisation of neonatal Staphylococcus capitis NRCS-A isolates compared with non NRCS-A Staphylococcus capitis from neonates and adults
Authors: Felgate Heather , Sethi Dheeraj , Faust Kirsten , Kiy Cemsid , Härtel Christoph , Rupp Jan , Clifford Rebecca , Dean Rachael , Tremlett Catherine , Wain John , Langridge Gemma , Clarke Paul , Page Andrew J. , Webber Mark A.
Published: October 2023

Staphylococcus capitis

is a frequent cause of late-onset sepsis in neonates admitted to Neonatal Intensive Care Units (NICU). One clone of

S. capitis

, NRCS-A has been isolated from NICUs globally although the reasons for the global success of this clone are not well understood.

We analysed a collection of

S. capitis

colonising babies admitted to two NICUs, one in the UK and one in Germany as well as corresponding pathological clinical isolates. Genome analysis identified a population structure of three groups; non-NRCS-A isolates, NRCS-A isolates, and a group of ‘proto NRCS-A’ – isolates closely related to NRCS-A but not associated with neonatal infection. All bloodstream isolates belonged to the NRCS-A group and were indistinguishable from strains carried on the skin or in the gut. NRCS-A isolates showed increased tolerance to chlorhexidine and antibiotics relative to the other

S. capitis

as well as enhanced ability to grow at higher pH values. Analysis of the pangenome of 138 isolates identified characteristic nsr and tarJ genes in both the NRCS-A and proto groups. A CRISPR-cas system was only seen in NRCS-A isolates which also showed enrichment of genes for metal acquisition and transport.

We found evidence for transmission of

S. capitis

NRCS-A within NICU, with related isolates shared between babies and multiple acquisitions by some babies. Our data show NRCS-A strains commonly colonise uninfected babies in NICU representing a potential reservoir for potential infection. This work provides more evidence that adaptation to survive in the gut and on skin facilitates spread of NRCS-A, and that metal acquisition and tolerance may be important to the biology of NRCS-A. Understanding how NRCS-A survives in NICUs can help develop infection control procedures against this clone.
Modeling spillover dynamics: understanding emerging pathogens of public health concern
Authors: Saldaña Fernando , Stollenwerk Nico , Bidaurrazaga Van-Dierdonck Joseba , Aguiar Maíra
Published: October 2023

The emergence of infectious diseases with pandemic potential is a major public health threat worldwide. According to the World Health Organization, around 60% of the reported emerging infectious diseases are zoonoses and have been triggered by spillover events. Although the dynamics of spillover events are not yet well understood, mathematical modeling has the potential to characterize the highly complex interactions among pathogens, wildlife, humans, and the environment where they coexist. In this work, motivated by discussions on the introductory phase of SARS-CoV-2 towards a pandemic scenario, we address the so far unexplored the emergence of novel infectious agents. Aiming at gaining insights into the dynamics of spillover events and the final outcome of an eventual disease outbreak in a population, we propose a continuous time stochastic modeling framework to describe a cross-species disease transmission by coupling the dynamics of animal reservoirs and human hosts. A complete analysis of the system is conducted, followed by numerical experiments where we investigate different scenarios of spillover events. Applied to the emergence of SARS-CoV-2 and monkeypox viruses, our results provide insights into the emergence of new infectious diseases able to cause not only local outbreaks but eventually explosive epidemics towards a pandemic.
Cerebral Visual Impairment: genetic diagnoses and phenotypic associations
Authors: Shaw Emogene ,   Genomics England Research Consortium, Flitcroft Ian , Bowman Richard , Baker Kate
Published: October 2023

Background

Cerebral visual impairment (CVI) is the commonest form of paediatric visual impairment in developed countries. CVI can arise from a host of genetic or acquired causes, but there has been limited research to date on CVI in the context of genetic disorders.

Methods

We carried out a retrospective analysis of genotypic and phenotypic data for participants with CVI within the DECIPHER database and 100,000 Genomes Project (100KGP).

Results

158 individuals with CVI were identified across both cohorts. Within this group, pathogenic or likely pathogenic sequence variants in 173 genes were identified. 25 of these genes already have known associations with CVI, whilst the remaining 148 are candidate genes for this phenotype. Gene Ontology analysis of the CVI gene sets from both DECIPHER and 100KGP suggest that CVI has a similar degree of genetic heterogeneity to other neurodevelopmental phenotypes, and a strong association with genetic variants converging on ion channels and receptor functions. Individuals with a monogenic disorder and CVI have a higher frequency of epilepsies and severe neurodisability than individuals with a monogenic disorder but not CVI.

Conclusion

This study supports the availability of genetic testing for individuals with CVI alongside other neurodevelopmental difficulties. It also supports the availability of ophthalmological screening for individuals with genetic diagnoses linked to CVI. Further studies could elaborate on the links between specific genetic disorders, visual maturation and broader neurodevelopmental characteristics.

What is known about the subject?

CVI is the most prevalent form of paediatric-onset visual impairment in the developed world.

CVI commonly occurs alongside other neurodevelopmental phenotypes such as epilepsies, global developmental delay, cerebral palsy, ADHD and autism.

CVI is known to have genetic aetiology, which is often undiagnosed.

What this study adds?

This study reports CVI-associated genetic diagnoses and phenotypic associations for two large cohorts

Gene ontology annotations have been analysed for candidate CVI genes

How this study might affect research, practice or policy

This study has implications for genetic testing in children with CVI

This study has implications for CVI screening in children with a genetic diagnosis
The Mediterranean Diet, Cardiometabolic Biomarkers, and Risk of All-Cause Mortality: A 25-Year Follow-Up Study of the Women’s Health Study
Authors: Ahmad Shafqat , Moorthy M. Vinayaga , Lee I-Min , Ridker Paul M , Manson JoAnn E. , Buring Julie , Demler Olga V. , Mora Samia
Published: October 2023

Background

Higher consumption of Mediterranean diet (MED) intake has been associated with reduced risk of all-cause mortality but limited data are available examining long-term outcomes in women or the underlying molecular mechanisms of this inverse association in human populations. We aimed to investigate the association of MED intake with long-term risk of all-cause mortality in women and to better characterize the relative contribution of traditional and novel cardiometabolic factors to the MED-related risk reduction in morality.

Methods

In a prospective cohort study of 25,315 initially healthy women from the Women’s Health Study, we assessed dietary MED intake using a validated semiquantitative food frequency questionnaire according to the usual 9-category measure of MED adherence. Baseline levels of more than thirty cardiometabolic biomarkers were measured using standard assays and targeted nuclear magnetic resonance spectroscopy, including lipids, lipoproteins, apolipoproteins, inflammation, glucose metabolism and insulin resistance, branched-chain amino acids, small metabolites, and clinical factors. Mortality and cause of death was ascertained prospectively through medical and death records.

Results

During a mean follow-up of 25 years, 3,879 deaths were ascertained. Compared to the reference group of low MED intake (0-3, approximately the bottom tertile), and adjusting for age, treatment, and energy intake, risk reductions were observed for the middle and upper MED groups with respective HRs of 0.84 (95% CI 0.78-0.90) and 0.77 (95% CI 0.70-0.84), p for trend <0.0001. Further adjusting for smoking, physical activity, alcohol intake and menopausal factors attenuated the risk reductions which remained significant with respective HRs of 0.92 (95% CI 0.85-0.99) and 0.89 (95% CI 0.82-0.98), p for trend 0.0011. Risk reductions were generally similar for CVD and non-CVD mortality. Small molecule metabolites (e.g., alanine and homocysteine) and inflammation made the largest contributions to lower mortality risk (accounting for 14.8% and 13.0% of the benefit of the MED-mortality association, respectively), followed by triglyceride-rich lipoproteins (10.2%), adiposity (10.2%) and insulin resistance (7.4%), with lesser contributions (<3%) from other pathways including branched-chain amino acids, high-density lipoproteins, low-density lipoproteins, glycemic measures, and hypertension.

Conclusions

In the large-scale prospective Women’s Health Study of 25,315 initially healthy US women followed for 25 years, higher MED intake was associated with approximately one fifth relative risk reduction in mortality. The inverse association was only partially explained by known novel and traditional cardiometabolic factors.
SERPINA11related novel Serpinopathy- a perinatal lethal disorder
Authors: Aggarwal Shagun , Vineeth Venugopal Satidevi , Padwal Shrutika S. , Bhat Sameer Ahmed , Singh Arpita , Kulkarni Aditya , Patil Mallikarjun , Tallapaka Karthik , Pasumarthi Divya , Venkatapuram Vijayasree , Dalal Ashwin , Bhandari Rashna
Published: October 2023

SERPINA11is a hitherto poorly characterised gene belonging to Clade A of the SERPIN superfamily. The exact functional significance and expression pattern of this gene remains unknown. Here we report a perinatal lethal phenotype associated with biallelic loss of function variants inSERPINA11, and characterised by gross and histopathological features of extracellular matrix disruption. We found SERPINA11 protein expression in multiple mouse tissues and human fetal lungs. Immunofluorescence of the affected fetal lung revealed markedly reduced expression of SERPINA11 protein compared with healthy, gestation matched human fetal lung. Protein expression data from HEK293T cell lines following site directed mutagenesis is also presented to support the loss of function nature of the variant. This novel serpinopathy appears to be a consequence of loss of inhibition of serine proteases involved in extracellular matrix remodelling, revealing SERPINA11 as a protease inhibitor critical for embryonic development.
Evaluating the Human Safety Net: Observational study of Physician Responses to Unsafe AI Recommendations in high-fidelity Simulation
Authors: Festor Paul , Nagendran Myura , Gordon Anthony C. , Faisal A. Aldo , Komorowski Matthieu
Published: October 2023

In the context of Artificial Intelligence (AI)-driven decision support systems for high-stakes environments, particularly in healthcare, ensuring the safety of human-AI interactions is paramount, given the potential risks associated with erroneous AI outputs. To address this, we conducted a prospective observational study involving 38 intensivists in a simulated medical setting.

Physicians wore eye-tracking glasses and received AI-generated treatment recommendations, including unsafe ones. Most clinicians promptly rejected unsafe AI recommendations, with many seeking senior assistance. Intriguingly, physicians paid increased attention to unsafe AI recommendations, as indicated by eye-tracking data. However, they did not rely on traditional clinical sources for validation post-AI interaction, suggesting limited “debugging.”

Our study emphasises the importance of human oversight in critical domains and highlights the value of eye-tracking in evaluating human-AI dynamics. Additionally, we observed human-human interactions, where an experimenter played the role of a bedside nurse, influencing a few physicians to accept unsafe AI recommendations. This underscores the complexity of trying to predict behavioural dynamics between humans and AI in high-stakes settings.