bluuebunny/crossref_metadata_2025 huggingface dataset:
Deep Brain Stimulator Device Infection: The Mayo Clinic Rochester Experience
Authors: Tabaja Hussam , Yuen Jason , Tai Don Bambino Geno , Campioli Cristina Corsini , Chesdachai Supavit , DeSimone Daniel C , Hassan Anhar , Klassen Bryan T , Miller Kai J , Lee Kendall H , Mahmood Maryam
Published: December 2022

Background

Deep brain stimulator (DBS)–related infection is a recognized complication that may significantly alter the course of DBS therapy. We describe the Mayo Clinic Rochester experience with DBS-related infections.

Methods

This was a retrospective study of all adults (≥18 years old) who underwent DBS-related procedures between 2000 and 2020 at the Mayo Clinic Rochester.

Results

There were 1087 patients who underwent 1896 procedures. Infection occurred in 57/1112 (5%) primary DBS implantations and 16/784 (2%) revision surgeries. The median time to infection (interquartile range) was 2.1 (0.9–6.9) months. The odds of infection were higher with longer operative length (P = .002), higher body mass index (BMI; P = .006), male sex (P = .041), and diabetes mellitus (P = .002). The association between infection and higher BMI (P = .002), male sex (P = .016), and diabetes mellitus (P = .003) remained significant in a subgroup analysis of primary implantations but not revision surgeries. Infection was superficial in 17 (23%) and deep in 56 (77%) cases. Commonly identified pathogens were Staphylococcus aureus (65%), coagulase-negative staphylococci (43%), and Cutibacterium acnes (45%). Three device management approaches were identified: 39 (53%) had complete device explantation, 20 (27%) had surgical intervention with device retention, and 14 (19%) had medical management alone. Treatment failure occurred in 16 (23%) patients. Time-to-event analysis showed fewer treatment failures with complete device explantation (P = .015). Only 1 individual had complications with brain abscess at failure.

Conclusions

Primary DBS implantations had higher rates of infection compared with revision surgeries. Complete device explantation was favored for deep infections. However, device salvage was commonly attempted and is a reasonable approach in select cases given the low rate of complications.
Evaluating Predictive Value of Surgical Resected Proximal Bone Margins in Diabetic Foot Osteomyelitis With Clinical Outcomes at 1 Year
Authors: Weng Bruce , Oskooilar Yasmin , Zakhary Bishoy , Chiu Chiao An , Wu Patrick , Mulligan Nikki , Sutjita Made
Published: December 2022

Background

Osteomyelitis of the diabetic foot remains a significant complication that may result in the need for amputation. Proximal surgical margin histopathology after limb-sparing amputation could be used to guide antimicrobial duration and prognostic management but remains debatable. Here we evaluate if negative proximal bone margins predict outcomes of diabetic foot osteomyelitis at 1 year.

Methods

A retrospective study assessed adults with diabetes undergoing limb-sparing foot amputations from September 2016 to September 2019. Patients required histopathology confirmation of osteomyelitis, proximal margin histopathology report, and documented electronic medical record follow-up through 12 months. The primary outcome evaluated if no further amputation at the same site was required in the following 12 months.

Results

Of 92 patients, 57 (61.9%) had pathology-confirmed negative margins for osteomyelitis. Patients with negative margins required less frequent subsequent amputations at the same site within 12 months compared to positive margins (86.0% vs 65.7%; P = .003). Antibiotic duration was shorter in patients with negative margins (mean, 18 vs 30 days; P = .001). Negative-margin patients also noted lower rates of readmission at 12 months (26.3% vs 51.4%; P = .015) for site-specific complications. Staphylococcus aureus was more predominant in patients with positive versus negative margins (57.1% vs 29.8%; P = .017).

Conclusions

Negative proximal bone margin by histopathology was associated with lower frequency of further amputations at the index surgical site within 12 months. This group also received shorter courses of antibiotic therapy. It was also associated with lower rates of readmission at 12 months for surgical-site complications. Proximal margin histopathology results potentially can be integrated to guide antimicrobial duration and decrease the frequency of further amputation at the original site.
Cost modelling incorporating procalcitonin for the risk stratification of febrile infants ≤60 days old
Authors: Dionisopoulos Zachary , Strumpf Erin , Anderson Gregory , Guigui Andre , Burstein Brett
Published: December 2022

Objectives

Procalcitonin testing is recommended to discriminate febrile young infants at risk of serious bacterial infections (SBI). However, this test is not available in many clinical settings, limited largely by cost. This study sought to evaluate contemporary real-world costs associated with the usual care of febrile young infants, and estimate impact on clinical trajectory and costs when incorporating procalcitonin testing.

Methods

We assessed hospital-level door-to-discharge costs of all well-appearing febrile infants aged ≤60 days, evaluated at a tertiary paediatric hospital between April/2016 and March/2019. Emergency Department and inpatient expense data for usual care were obtained from the institutional general ledger, validated by the provincial Ministry of Health. These costs were then incorporated into a probabilistic model of risk stratification for an equivalent simulated cohort, with the addition of procalcitonin.

Results

During the 3-year study period, 1168 index visits were included for analysis. Real-world median costs-per-infant were the following: $3266 (IQR $2468 to $4317, n=93) for hospitalized infants with SBIs; $2476 (IQR $1974 to $3236, n=530) for hospitalized infants without SBIs; $323 (IQR $286 to $393, n=538) for discharged infants without SBIs; and, $3879 (IQR $3263 to $5297, n=7) for discharged infants subsequently hospitalized for missed SBIs. Overall median cost-per-infant of usual care was $1555 (IQR $1244 to $2025), compared to a modelled cost of $1389 (IQR $1118 to $1797) with the addition of procalcitonin (10.7% overall cost savings; $1,816,733 versus $1,622,483). Under pessimistic and optimistic model assumptions, savings were 5.9% and 14.9%, respectively.

Conclusions

Usual care of febrile young infants is variable and resource intensive. Increased access to procalcitonin testing could improve risk stratification at lower overall costs.
Perceived barriers to the provision of adolescent confidential care in a tertiary care setting
Authors: Agostino Holly , Burstein Brett
Published: December 2022

Objective

Adolescents are more likely to seek care and disclose sensitive health information if confidentiality is assured. Little is known regarding the provision of confidential care to adolescents in the hospital setting. We sought to understand confidentiality practices and barriers for adolescents cared for in a tertiary hospital setting.

Methods

This was a cross-sectional survey of all Emergency Department (ED), hospitalist, and resident physicians at a tertiary paediatric hospital from May/2019 to July/2019. Participants were asked multiple choice questions regarding practices, comfort, and barriers to confidential care.

Results

Response rate was 91% (n = 72/79; 26 ED, 14 hospitalists, 32 residents). Overall, 47% of respondents doubted that confidential care was being consistently provided to adolescents. Fifty-eight per cent of attendings and 31% of residents reported usually/always offering confidential care. Factors most reported to influence the provision of confidential care were chief complaint (75%), time of visit (45%), and patient age (25%). Barriers to the quantity or quality of confidential care were identified by 89%, most commonly including time constraints (21%), perceived parental resistance (26%), lack of private space (26%), and the belief that confidentiality is not necessary for all adolescent encounters (34%). Forty per cent of respondents reported breaching confidentially and discussing sensitive topics with adolescents in front of family members. Overall, only 45% felt they had received adequate training on how best to deliver confidential care, and 75% reported a desire for additional training.

Conclusion

Results suggest inadequate provision of confidential care in a tertiary teaching hospital, with several potentially modifiable barriers.
A synthesis of the biogeographical distribution of Rotifera in Africa
Authors: Smolak Radoslav , Walsh Elizabeth J , Brown Patrick D , Wallace Robert L
Published: December 2022

The rotifer fauna of Africa has been studied for >100 years, but there has been no recent synthesis. We compiled data from 265 publications that reported information on African rotifers. Our dataset yielded information on the distribution of 765 taxa from ~1850 separate sites; these included both natural and artificial habitats such as lakes, ponds, puddles, oases, artificial systems, rivers and wetlands. A heat map of predicted rotifer biodiversity indicated that the greatest diversity should be present in the sub-Saharan region including a large hotspot in Mali and several smaller ones scattered in that region. Lakes Kariba, Tanganyika and Malawi showed high-predicted diversity, but surprisingly, Lake Victoria had lower diversity than expected. Two regions showed unusually high-predicted diversity: northwestern Algeria extending into Morocco and Egypt. Equatorial Africa is rich in habitats well suited for rotifers, yet their predicted biodiversity seems low. Latitude and elevation were negatively correlated with richness, while permanent water source and littoral zone were positively correlated according to generalized linear modeling results. Partial RDA analyses showed significant correlations among several environmental features and species occurrences. It is clear that more survey work remains to be done to achieve a better understanding of African rotifers.
Freezing Biological Time: A Modern Perspective on Organ Preservation
Authors: Criswell Tracy , Swart Corné , Stoudemire Jana , Brockbank Kelvin G M , Powell-Palm Matthew , Stilwell Reginald , Floren Michael
Published: December 2022

Transporting tissues and organs from the site of donation to the patient in need, while maintaining viability, is a limiting factor in transplantation medicine. One way in which the supply chain of organs for transplantation can be improved is to discover novel approaches and technologies that preserve the health of organs outside of the body. The dominant technologies that are currently in use in the supply chain for biological materials maintain tissue temperatures ranging from a controlled room temperature (+25 °C to +15 °C) to cryogenic (−120 °C to −196 °C) temperatures (reviewed in Criswell et al. Stem Cells Transl Med. 2022). However, there are many cells and tissues, as well as all major organs, that respond less robustly to preservation attempts, particularly when there is a need for transport over long distances that require more time. In this perspective article, we will highlight the current challenges and advances in biopreservation aimed at “freezing biological time,” and discuss the future directions and requirements needed in the field.
Performance of Akaike Information Criterion and Bayesian Information Criterion in Selecting Partition Models and Mixture Models
Authors: Liu Qin , Charleston Michael A , Richards Shane A , Holland Barbara R
Published: December 2022

In molecular phylogenetics, partition models and mixture models provide different approaches to accommodating heterogeneity in genomic sequencing data. Both types of models generally give a superior fit to data than models that assume the process of sequence evolution is homogeneous across sites and lineages. The Akaike Information Criterion (AIC), an estimator of Kullback–Leibler divergence, and the Bayesian Information Criterion (BIC) are popular tools to select models in phylogenetics. Recent work suggests that AIC should not be used for comparing mixture and partition models. In this work, we clarify that this difficulty is not fully explained by AIC misestimating the Kullback–Leibler divergence. We also investigate the performance of the AIC and BIC at comparing amongst mixture models and amongst partition models. We find that under nonstandard conditions (i.e. when some edges have small expected number of changes), AIC underestimates the expected Kullback–Leibler divergence. Under such conditions, AIC preferred the complex mixture models and BIC preferred the simpler mixture models. The mixture models selected by AIC had a better performance in estimating the edge length, while the simpler models selected by BIC performed better in estimating the base frequencies and substitution rate parameters. In contrast, AIC and BIC both prefer simpler partition models over more complex partition models under nonstandard conditions, despite the fact that the more complex partition model was the generating model. We also investigated how mispartitioning (i.e., grouping sites that have not evolved under the same process) affects both the performance of partition models compared with mixture models and the model selection process. We found that as the level of mispartitioning increases, the bias of AIC in estimating the expected Kullback–Leibler divergence remains the same, and the branch lengths and evolutionary parameters estimated by partition models become less accurate. We recommend that researchers are cautious when using AIC and BIC to select among partition and mixture models; other alternatives, such as cross-validation and bootstrapping, should be explored, but may suffer similar limitations [AIC; BIC; mispartitioning; partitioning; partition model; mixture model].
The protective effect of red cabbage on water-soluble fractions of spent crankcase oil-induced alterations in lipid function biomarkers and atherogenic indices in male Albino rats
Authors: Bekibele G E , Anacletus F C , Patrick-Iwuanyanwu K C , Nwaogazie I L
Published: December 2022

Spent crankcase oil (SCO) contains a cocktail of metals and polycyclic aromatic hydrocarbons (PAHs), transferred to the associated water-soluble fractions (WSF); and low-dose heavy metals exposures could increase the triglycerides (TG), total cholesterol (TC), low-density lipoproteins (LDL), and very-low-density lipoproteins (VLDL) concentrations. Hence, this study estimated the changes in the lipid profile and atherogenic indices (AI) of male Wistar albino rats exposed to the WSF of SCO and treated with aqueous extracts (AE) of red cabbage (RC) for 60 and 90 days. Sixty-four male Wistar rats divided into 8 groups (8 animals each) were orally administered 1 mL of deionized water, 500 mg/kg AE of RC, 1 mL of 25%, 50%, and 100% WSF of SCO daily for 60 and 90 days, whereas alternate groups were given the stated percentages of the WSF and the AE. Serum TG, TC, LDL, and VLDL concentrations were then analyzed using appropriate kits and the AI estimated thereafter. Although the 60 days study presented a nonsignificant (P < 0.05) difference in the TG, VLDL, and high density lipoprotein (HDL)-C levels in all the exposed and treated groups, a significantly (P < 0.05) elevated TC and non-HDL was recorded for the 100% exposed group alone. Also, the LDL concentration of all exposed groups was higher than all treated groups. The findings at the 90th day was different, such that the 100% and 25% exposed only groups had elevated lipid profile (except HDL-C) concentrations and AI compared with other groups. RC extracts can act as good hypolipidemic agents in WSF of SCO hyperlipidemia potentiating events.
Initial Outcomes of a Novel Modification of Looped Threaded Carpal Tunnel Release Method
Authors: Biglari Farsad , Sabaghzadeh Amir , Sadighi Mehrdad , Ebrahimpour Adel , Davoodi Bojd Maryam , Jafari Kafiabadi Meisam
Published: December 2022

Various surgical techniques are available for the alleviation of symptoms in carpal tunnel syndrome and each of them has its pros and cons. This study was designed and performed to present a novel approach for cutting transverse carpal ligament by the thread looping technique without the use of ultrasonography. The novel modification of looped threaded carpal tunnel release was performed on 10 hands of 10 patients. The disabilities of arm, shoulder, and hand score, visual analog scale, and 2-point discrimination were used for assessing the outcomes. No patients developed pillar pain or scar discomfort after surgery. Complete elimination of paresthesia, pain, and numbness occurred in all patients. There was a significant reduction in the disabilities of arm, shoulder, and hand and visual analog scale scores (P value<0.05). This technique is safe, available, and effective for carpal tunnel release and minimizes postoperative complications, such as pillar pain, and scar discomfort with avoiding unnecessary injuries to the surrounding soft tissue.
Single-Center Experience Using the Cardiohelp System for Neonatal and Pediatric Extracorporeal Membrane Oxygenation
Authors: Agasthya Nisha , Froehlich Curtis D. , Golecki Michael , Meyer Marisa , Ogino Mark T. , Froehlich Kendra , Beaty Christopher , McCants Sharon , Maul Timothy M. , Dirnberger Daniel R.
Published: December 2022

OBJECTIVES:

Extracorporeal membrane oxygenation (ECMO) systems have continued to evolve and improve with the development of smaller and portable systems. The Cardiohelp (Maquet Getinge Cardiopulmonary AG, Rastatt, Germany) portable life support device is a compact ECMO system used widely in adults and for ECMO transport. Reports of its use in neonatal and pediatric centers remain limited. In this single-center retrospective review, we describe our institutional experience with the Cardiohelp.

DESIGN:

Single-center retrospective review.

SETTING:

Neonatal ICUs and PICUs in a tertiary-care children’s hospital.

PATIENTS:

Seventeen pediatric patients on ECMO.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Median (interquartile range, IQR) of patient age was 0.5 years (0–7 yr). Eleven of 17 patients were on veno-arterial ECMO, five on veno-venous ECMO, and one on veno-venoarterial ECMO. All veno-venous and veno-venoarterial runs (n = 6) were accomplished with bicaval, dual-lumen cannulae. Median duration on Cardiohelp was 113 hours (IQR 50–140 hr). Median anti-Xa level for patients was 0.43 IU/mL (IQR 0.35–0.47 IU/mL), with median heparin dose of 23.6 U/kg/hr (IQR 17.6–28.1 U/kg/hr). Median plasma-free hemoglobin was 41.4 mg/dL (IQR 30–60 mg/dL). Circuit change was required in three cases. Fourteen patients survived ECMO, with 13 patients surviving to discharge.

CONCLUSIONS:

We have used the Cardiohelp system to support 17 neonatal and pediatric ECMO patients, without complications. Further studies are warranted to compare complications, outcomes, and overall cost with other institutions and other existing ECMO systems.
Alteration in shear wave elastography is associated with acute kidney injury: A prospective observational pilot study
Authors: Xu Qiancheng , Qiang Banghong , Pan Youjun , Li Juan , Zha Lei , Lu Weihua , Wang Junli , Li Jianguo
Published: December 2022

Background

Kidney stiffness could change during kidney disease. We hypothesize that acute kidney injury (AKI) would increase renal stiffness. Therefore, evaluating kidney Young's modulus (YM, a measure of tissue stiffness) using shear wave elastography (SWE) might help to diagnose AKI.

Methods

This research was divided into two studies. Study A: Male C57BL/6 mice were used to observe kidney YM changes induced by sepsis-associated AKI, which was established by caecal ligation and puncture (CLP). Study B included 54 consecutive critically ill patients with or without AKI. Changes in renal YM were observed.

Results

Study A: CLP mice showed a significantly higher kidney YM compared to the sham group. The YM gradually increased from CLP 0-hour to CLP 24 hours. And, presented a fair relationship with the renal tubular injury score (R2 = 0.71) and serum creatinine (R2 = 0.73). Study B: YM was easily accessible and the intraclass correlation coefficient ranged from 0.62 to 0.84. Kidney YM was higher in AKI patients and gradually increased from non-AKI to AKI III patients. Furthermore, the YM in the upper, middle and lower poles renal cortex presented a fair relationship with kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin (R2 ranging from 0.4 to 0.58). And the area under curves of the above five indicators for the diagnosis of AKI were 0.7, 0.73, 0.70, 0.74, and 0.79, respectively.

Conclusions

SWE-derived estimates of renal stiffness are higher in AKI patients and sepsis-associated AKI mice. However, it has no advantage over NGAL and KIM-1.

Trial registration: Chinese Clinical Trial Registry No: ChiCTR2200061725. Retrospectively registered on 1 July 2022, https://www.chictr.org.cn/showproj.aspx?proj=169359
Successful Islet Transplantation Into a Subcutaneous Polycaprolactone Scaffold in Mice and Pigs
Authors: Smink Alexandra M. , Rodriquez Samuel , Li Shiri , Ceballos Bryan , Corrales Nicole , Alexander Michael , Koster Taco , de Haan Bart J. , Lakey Jonathan R.T. , de Vos Paul
Published: December 2022

Background.

Islet transplantation is a promising treatment for type 1 diabetes. It has the potential to improve glycemic control, particularly in patients suffering from hypoglycemic unawareness and glycemic instability. As most islet grafts do not function permanently, efforts are needed to create an accessible and replaceable site, for islet grafts or for insulin-producing cells obtained from replenishable sources. To this end, we designed and tested an artificial, polymeric subcutaneous transplantation site that allows repeated transplantation of islets.

Methods.

In this study, we developed and compared scaffolds made of poly(D,L,-lactide-co-ε-caprolactone) (PDLLCL) and polycaprolactone (PCL). Efficacy was first tested in mice‚ and then, as a proof of principle for application in a large animal model, the scaffolds were tested in pigs, as their skin structure is similar to that of humans.

Results.

In mice, islet transplantation in a PCL scaffold expedited return to normoglycemia in comparison to PDLLCL (7.7 ± 3.7 versus 16.8 ± 6.5 d), but it took longer than the kidney capsule control group. PCL also supported porcine functional islet survival in vitro. Subcutaneous implantation of PDLLCL and PCL scaffolds in pigs revealed that PCL scaffolds were more stable and was associated with less infiltration by immune cells than PDLLCL scaffolds. Prevascularized PCL scaffolds were therefore used to demonstrate the functional survival of allogenic islets under the skin of pigs.

Conclusions.

To conclude, a novel PCL scaffold shows efficacy as a readily accessible and replaceable, subcutaneous transplantation site for islets in mice and demonstrated islet survival after a month in pigs.
Australian Donation and Transplantation Biobank: A Research Biobank Integrated Within a Deceased Organ and Tissue Donation Program
Authors: Sharma Varun J. , Starkey Graham , D’Costa Rohit , James Fiona , Mouhtouris Effie , Davis Lisa , Wang Boa Zhong , Vago Angela , Raman Jaishankar , Mackay Laura K. , Opdam Helen , Jones Robert , Grayson M. Lindsay , Martin Dominique E. , Gordon Claire L.
Published: December 2022

Background.

We aimed to facilitate the donation of tissue samples for research by establishing a centralized system integrated in the organ donation program for collection, storage, and distribution of samples (the Australian Donation and Transplantation Biobank [ADTB]).

Methods.

Feasibility of a research biobank integrated within the deceased organ and tissue donation program was assessed. DonateLife Victoria sought consent for ADTB donation after consent was received for organ donation for transplantation from the donor’s senior available next of kin. ADTB samples were collected during donation surgery and distributed fresh to researchers or stored for future research. The main outcome measures were ADTB donation rates, ADTB sample collection, ADTB sample use, and to identify ethical considerations.

Results.

Over 2 y, samples were collected for the ADTB from 69 donors (28% of 249 donors). Samples were obtained from the spleen (n = 59, 86%), colon (n = 57, 83%), ileum (n = 56, 82%), duodenum (n = 55, 80%), blood (n = 55, 80%), bone marrow (n = 55, 80%), skin (n = 54, 78%), mesenteric lymph nodes (n = 56, 81%), liver (n = 21, 30%), lung (n = 29, 42%), and lung-draining lymph node (n = 29, 42%). Heart (n = 20), breast (n = 1), and lower urinary tract (n = 1) samples were obtained in the second year. Five hundred fifty-six samples were used in 19 ethics-approved research projects spanning the fields of immunology, microbiology, oncology, anatomy, physiology, and surgery.

Conclusions.

The integration of routine deceased donation and transplantation activities with a coordinated system for retrieval and allocation of donor samples for use in a range of research projects is feasible and valuable.
Transplantation Amid a Pandemic: The Fall and Rise of Kidney Transplantation in the United States
Authors: Bisen Shivani S. , Zeiser Laura B. , Boyarsky Brian , Werbel William , Snyder Jon , Garonzik-Wang Jacqueline , Levan Macey L. , Segev Dorry L. , Massie Allan B.
Published: December 2022

Background.

Following the outbreak of coronavirus disease 2019 (COVID-19) in the United States, the number of kidney waitlist additions and living-donor and deceased-donor kidney transplants (LDKT/DDKT) decreased substantially but began recovering within a few months. Since then, there have been several additional waves of infection, most notably, the Delta and Omicron surges beginning in August and December 2021, respectively.

Methods.

Using SRTR data, we compared observed waitlist registrations, waitlist mortality, waitlist removal due to deteriorating condition, LDKT, and DDKT over 5 distinct pandemic periods to expected events based on calculations from preepidemic data while accounting for seasonality and secular trends.

Results.

Although the number of daily waitlist additions has been increasing since May 2020, the size of the active waitlist has consistently declined, reaching a minimum of 52 556 on February 27, 2022. The recent Omicron surge knocked LDKT from 25% below baseline (incidence rate ratio [IRR] = 0.690.750.81) during the Delta wave to 38% below baseline (IRR = 0.580.620.67). DDKT, however, was less affected by the Omicron wave (IRR = 0.850.890.93 and 0.880.920.96 during the Delta and Omicron waves, respectively). Waitlist death decreased from 56% above baseline (IRR = 1.431.561.70) during Delta to 41% above baseline during Omicron, whereas waitlist removal due to deteriorating condition remained at baseline/expected levels during the Delta wave (IRR = 0.931.021.12) and the Omicron wave (IRR = 0.991.071.16).

Conclusions.

Despite exceptionally high COVID-19 incidence during the Omicron wave, the transplant system responded similarly to prior waves that imposed a lesser disease burden, demonstrating the transplant system’s growing adaptations and resilience to this now endemic disease.
Concepts in interaction: social engagement and inner experiences
Authors: Borghi Anna M. , Osińska Albertyna , Roepstorff Andreas , Raczaszek-Leonardi Joanna
Published: December 2022

This theme issue aims to view the literature on concepts through a novel lens, that of social interaction and its influence on inner experiences. It discusses unsolved problems in literature on concepts, emphasizing the distinction between concrete versus abstract concepts and external versus internal grounding. This introductory article reflects the two research streams that the theme aims to bridge—in this area, the dimension of embodied interaction with others and how this influences the interaction with ourselves is still underexplored. In the first part, we discuss recent trends in social cognition, showing how interacting with others influences our concepts. In the second part, we address how social interactions become part of our inner world in a Vygotskian fashion. First, we illustrate how interoception, emotion and metacognition are connected with concepts and knowledge. Second, we deal with how language, in both its outer and inner form, can empower cognition and concepts. We also briefly describe how novel experimental and computational methods contribute to investigating the online use of concepts. Overall, this introductory article outlines the potentialities of an integrated and interactive approach that can give new, fresh life to a topic, that of concepts, which lies at the root of human cognition.

This article is part of the theme issue ‘Concepts in interaction: social engagement and inner experiences’.
On the social nature of abstraction: cognitive implications of interaction and diversity
Authors: Olsen Karsten , Tylén Kristian
Published: December 2022

The human capacity for abstraction is remarkable. We effortlessly form abstract representations from varied experiences, generalizing and flexibly transferring experiences and knowledge between contexts, which can facilitate reasoning, problem solving and learning across many domains. The cognitive process of abstraction, however, is often portrayed and investigated as an individual process. This paper addresses how cognitive processes of abstraction—together with other aspects of human reasoning and problem solving—are fundamentally shaped and modulated by online social interaction. Starting from a general distinction between convergent thinking, divergent thinking and processes of abstraction, we address how social interaction shapes information processing differently depending on cognitive demands, social coordination and task ecologies. In particular, we suggest that processes of abstraction are facilitated by the interactive sharing and integration of varied individual experiences. To this end, we also discuss how the dynamics of group interactions vary as a function of group composition; that is, in terms of the similarity and diversity between the group members. We conclude by outlining the role of cognitive diversity in interactive processes and consider the importance of group diversity in processes of abstraction.

This article is part of the theme issue ‘Concepts in interaction: social engagement and inner experiences’.
The RNA-binding protein Adad1 is necessary for germ cell maintenance and meiosis in zebrafish
Authors: Islam Kazi Nazrul , Ajao Anuoluwapo , Henke Katrin , Siegfried Kellee R.
Published: December 2022

The double stranded RNA binding protein Adad1 (adenosine deaminase domain containing 1) is a member of theadenosinedeaminaseacting onRNAs (Adar) protein family with germ cell-specific expression. In mice, Adad1 is necessary for sperm differentiation, however its function outside of mammals has not been investigated. Here, through an N-ethyl-N-nitrosourea (ENU) based forward genetic screen, we identified anadad1mutant zebrafish line that develop as sterile males. Further histological examination revealed complete lack of germ cells in adult mutant fish, however germ cells populated the gonad, proliferated, and entered meiosis in larval and juvenile fish. Although meiosis was initiated inadad1mutant testes, the spermatocytes failed to progress beyond the zygotene stage. Thus, Adad1 is essential for meiosis and germline maintenance in zebrafish. We tested if spermatogonial stem cells were affected using a label retaining cell (LRC) assay and found that the mutant testes had fewer LRCs compared to wild-type siblings, suggesting that failure to maintain the spermatogonial stem cells resulted in germ cell loss by adulthood. To identify potential molecular processes regulated by Adad1, we sequenced bulk mRNA from mutants and wild-type testes and found mis-regulation of genes involved in RNA stability and modification, pointing to a potential broader role in post-transcriptional regulation. Our findings suggest that Adad1 is an RNA regulatory protein required for fertility through regulation of spermatogonial stem cell maintenance in zebrafish.

Author Summary

Infertility is a serious problem for millions of couples who wish to have children. Globally more than 10% of couples suffer from infertility due to genetic, epigenetic, and environmental factors. Among these about 50% of cases occur due to genetic factors such as aneuploidy and genetic mutations affecting development of the gametes (i.e. sperm and eggs). Although many genes are known to be involved in germ cell development, genetic causes of infertility are still largely unexplained. Therefore, it is imperative to investigate genes involved in reproductive processes. In this study, we report that theadad1gene is essential for germ cell maintenance and fertility in zebrafish. Our analysis of zebrafishadad1mutants demonstrates that it is required for maintenance of the germline stem cells and for completion of meiosis. This is in contrast to mouseAdad1, which functions later in gamete development to regulate differentiation of haploid sperm. Our work on zebrafishadad1has uncovered previously unknown roles ofadad1function in germline stem cell maintenance.
Utilizing Electronic Health Records (EHR) and Tumor Panel Sequencing to Demystify Prognosis of Cancer of Unknown Primary (CUP) patients
Authors: Moon Intae , LoPiccolo Jaclyn , Baca Sylvan C. , Sholl Lynette M. , Kehl Kenneth L. , Hassett Michael J. , Liu David , Schrag Deborah , Gusev Alexander
Published: December 2022

When a standardized diagnostic test fails to locate the primary site of a metastatic cancer, it is diagnosed as a cancer of unknown primary (CUP). CUPs account for 3-5% of all cancers but do not have established targeted therapies, leading to typically dismal outcomes. Here, we develop OncoNPC, a machine learning classifier of CUP, trained on targeted next generation sequencing data from 34,567 tumors across 22 primary cancer types collected as part of routine clinical care at three institutions under AACR Project GENIE initiative [1]. OncoNPC achieved a weighted F1 score of 0.94 for high confidence predictions on known cancer types (65% of held-out samples). To evaluate its clinical utility, we applied OncoNPC to 971 CUP tumor samples from patients treated at the Dana-Farber Cancer Institute (DFCI). OncoNPC CUP subtypes exhibited significantly different survival outcomes, and identified potentially actionable molecular alterations in 23% of tumors. Importantly, patients with CUP, who received first palliative intent treatments concordant with their OncoNPC predicted sites, showed significantly better outcomes (Hazard Ratio 0.348, 95% C.I. 0.210 - 0.570, p-value 2.32×10−5) after accounting for potential measured confounders. As validation, we showed that OncoNPC CUP subtypes exhibited significantly higher polygenic germline risk for the predicted cancer type. OncoNPC thus provides evidence of distinct CUP subtypes and offers the potential for clinical decision support for managing patients with CUP.
Seroprevalence of anti-SARS-CoV-2 antibodies before and after implementation of anti-COVID-19 vaccination among hospital staff in Bangui, Central African Republic
Authors: Manirakiza Alexandre , Malaka Christian , Mossoro-Kpinde Hermione Dahlia , Yambiyo Brice Martial , Mossoro-Kpinde Christian Diamant , Fandema Emmanuel , Yakola Christelle Niamathe , Doyama-Woza Rodrigue , Kangale-Wando Ida Maxime , Komba Elliot Kosh , Nzapali Guiagassomon Sandra Manuella Bénedicte , de la Grace Namsenei-Dankpea Lydie Joella-Venus , Gomelle Coti-Reckoundji Cathy Sandra , Bouhouda Modeste , Gody Jean-Chrisostome , Grésenguet Gérard , Vernet Guy , Vernet Marie-Astrid , Nakoune Emmanuel
Published: December 2022

Introduction

Healthcare workers (HCWs) are at high to very high risk for SARS-CoV-2 infection. The persistence of this pandemic worldwide has instigated the need for an investigation of the level of prevention through immunization and vaccination against SARS-CoV-2 among HCWs. The objective of our study was to evaluate any changes in anti-COVID-19 serological status before and after the vaccination campaign of health personnel in the Central African Republic.

Method

We carried out a repeated cross-sectional serological study on HCWs at the university hospital centers of Bangui. Blood samples were collected and tested for anti-SARS-CoV-2 IgM and IgG using the ELISA technique on blood samples.

Results

A total of 179 and 141 HCWs were included in the first and second surveys, respectively. Of these staff, 31.8% of HCWs were positive for anti-SARS-CoV-2 IgG in the first survey, whereas 95.7% were positive for anti-SARS-CoV-2 IgG in the second survey. However, the proportion of HCWs positive for SARS-CoV-2 IgM antibodies was low (9.7% in the first survey and 3.6% in the second survey).

Conclusion

These findings showed a sharp increase in seroprevalence over a one-year period. This increase is primarily due to the synergistic effect of the infection and the implementation of vaccines against COVID-19. Further studies to assess the persistence of anti-SARS-CoV-2 antibodies are needed.
Sex-specific DNA methylation in saliva from the multi-ethnic Fragile Families and Child Wellbeing Study
Authors: Reiner Allison , Bakulski Kelly M. , Fisher Jonah D. , Dou John F. , Schneper Lisa , Mitchell Colter , Notterman Daniel A. , Zawistowski Matthew , Ware Erin B.
Published: December 2022

The prevalence of many diseases differs by sex, potentially due to sex-specific patterns in DNA methylation. Autosomal sex-specific differences in DNA methylation have been observed in cord blood and placental tissue, but are not well studied in saliva or in diverse populations. We sought to characterize sex-specific DNA methylation on autosomal chromosomes in saliva samples from children in the Fragile Families and Child Wellbeing Study, a multi-ethnic prospective birth cohort containing an oversampling of Black, Hispanic and low-income families. DNA methylation from saliva samples were analyzed on 796 children at both ages 9 and 15 with DNA methylation measured using the Illumina HumanMethylation 450k array. An epigenome-wide association analysis of the age 9 samples identified 8,430 sex-differentiated autosomal DNA methylation sites at age 9 (P < 2.4×10−7), of which 76.2% had higher DNA methylation in female children. The strongest sex-difference was in the cg26921482 probe, in theAMDHD2gene, with 30.6% higher DNA methylation in female compared to male children (P < 1×10−300). Treating the age 15 samples as an internal replication set, we observed highly consistent results between the age 9 and age 15 measurements, indicating stable and replicable sex-differentiation. Further, we directly compared our results to previously published DNA methylation sex differences in both cord blood and saliva and again found strong consistency. Our findings support widespread and robust sex-differential DNA methylation across age, human tissues, and populations. These findings help inform our understanding of potential biological processes contributing to sex differences in human physiology and disease.
Paf1 complex subunit Rtf1 stimulates H2B ubiquitylation by interacting with the highly conserved N-terminal helix of Rad6
Authors: Fetian Tasniem , McShane Brendan M. , Horan Nicole L. , Shodja Donya N. , True Jason D. , Mosley Amber L. , Arndt Karen M.
Published: December 2022

Histone modifications coupled to transcription elongation play important roles in regulating the accuracy and efficiency of gene expression. The mono-ubiquitylation of a conserved lysine in H2B (K123 inSaccharomyces cerevisiae; K120 in humans) occurs co-transcriptionally and is required for initiating a histone modification cascade on active genes. H2BK123 ubiquitylation (H2BK123ub) requires the RNA polymerase II (RNAPII)-associated Paf1 transcription elongation complex (Paf1C). Through its Histone Modification Domain (HMD), the Rtf1 subunit of Paf1C directly interacts with the ubiquitin conjugase Rad6, leading to the stimulation of H2BK123ubin vivoandin vitro. To understand the molecular mechanisms that target Rad6 to its histone substrate, we identified the site of interaction for the HMD on Rad6. Usingin vitrocrosslinking followed by mass spectrometry, we localized the primary contact surface for the HMD to the highly conserved N-terminal helix of Rad6. Using a combination of genetic and biochemical experiments, we identified separation-of-function mutations inS. cerevisiae RAD6that greatly impair H2BK123 ubiquitylation but not other Rad6 functions. Finally, by employing RNA-sequencing as a sensitive approach for comparing mutant phenotypes, we show that mutating either side of the proposed Rad6-HMD interface yields strikingly similar transcriptome profiles that extensively overlap with those of a mutant that lacks the site of ubiquitylation in H2B. Our results fit a model in which a specific interface between a transcription elongation factor and a ubiquitin conjugase guides substrate selection toward a highly conserved chromatin target during active gene expression.

Significance Statement

Transcription by RNAPII is tightly coordinated with mechanisms that control chromatin structure. Disruption of this interplay leads to deleterious effects on gene expression and genome architecture. Proteins that associate with RNAPII during transcription elongation play an important role in coupling histone modifications to active transcription. Paf1C, a conserved member of the RNAPII active elongation complex, is required for the ubiquitylation of histone H2B, a modification with effects on nucleosome stability and the methylation and acetylation state of chromatin. Here, we provide new insights into how a conserved domain in Paf1C, which we previously showed to be necessary and sufficient for Paf1C-mediated stimulation of H2B ubiquitylation, interacts with the ubiquitin conjugase for H2B thereby guiding its specificity.
Identifying efficient linkage strategies for HIV self-testing (IDEaL): a study protocol for an individually randomized control trial
Authors: Dovel Kathryn , Balakasi Kelvin , Hubbard Julie , Phiri Khumbo , Nichols Brooke E. , Coates Thomas J. , Kulich Michal , Chikuse Elijah , Phiri Sam , Long Lawrence , Hoffman Risa , Choko Augustine
Published: December 2022

Introduction

Men in sub-Saharan Africa are less likely than women to initiate antiretroviral therapy (ART) and are more likely to have longer cycles of disengagement from ART programs. Treatment interventions that meet the unique needs of men are needed, but they must be scalable. We will conduct a study to test the impact of various interventions on six-month retention in ART programs among men living with HIV who are not currently engaged in care.

Methods and Analysis

We will conduct a programmatic, individually randomized, non-blinded, non-inferiority controlled trial. “Non-engaged” men will be randomized 1:1:1 to either a Stepped, Low-Intensity, or High-Intensity arm. In the Stepped arm, intervention activities build in intensity over time for those who do not reengage in care with the following steps: 1) one-time male-specific counseling + facility navigation ⟶ 2) ongoing male mentorship + facility navigation ⟶ outside-facility ART initiation + male-specific counseling + facility navigation for follow-up ART visits. The Low-Intensity Intervention includes one-time male-specific counseling + facility navigation only and the High-Intensity Intervention offers immediate outside-facility ART initiation + male-specific counseling + facility navigation for follow-up ART visits. Our primary outcome is 6-month retention in care. Secondary outcomes include cost-effectiveness and rates of adverse events.

Ethics and Dissemination

The Institutional Review Board of the University of California, Los Angeles and the National Health Sciences Research Council in Malawi have approved the trial protocol. Findings will be disseminated rapidly in national and international forums, as well as in peer-reviewed journals and are expected to provide urgently needed information to other countries and donors.

ARTICLE SUMMARY

Strengths and limitations

IDEAL provides male-specific differentiated models of care aimed to improve men’s ART outcomes. We specifically focus on building trusting relationships with health care workers and developing client-led, individualized strategies to overcome barriers to care.

IDEAL will test the impact of a stepped intervention for men. This approach promises to improve the efficiency and reach of HIV programs for men as the highest-resource interventions will only be received by the minority of men who are most in need.

IDEAL develops and tests male-specific counseling curriculum that, if effective, could easily be taken to scale. Findings from the study will identify critical components for male-specific counseling, especially among men who struggle to be retained in HIV care.
chiLife: An open-source Python package forin silicospin labeling and integrative protein modeling
Authors: Tessmer Maxx H. , Stoll Stefan
Published: December 2022

Here we introduce chiLife, a Python package for site-directed spin label (SDSL) modeling for electron paramagnetic resonance (EPR) spectroscopy, in particular double electron–electron resonance (DEER). It is based on in silico attachment of rotamer ensemble representations of spin labels to protein structures. chiLife enables the development of custom protein analysis and modeling pipelines using SDSL EPR experimental data. It allows the user to add custom spin labels, scoring functions and spin label modeling methods. chiLife is designed with integration into third-party software in mind, to take advantage of the diverse and rapidly expanding set of molecular modeling tools available with a Python interface. This article describes the main design principles of chiLife and presents a series of examples.

Author summary

Thanks to modern modeling methods like AlphaFold2, RosettaFold, and ESMFold, high-resolution structural models of proteins are widely available. While these models offer insight into the structure and function of biomedically and technologically significant proteins, most of them are not experimentally validated. Furthermore, many proteins exhibit functionally important conformational flexibility that is not captured by these models. Site-directed spin labeling (SDSL) electron paramagnetic resonance (EPR) spectroscopy is a powerful tool for probing protein structure and conformational heterogeneity, making it ideal for validating, refining, and expanding protein models. To extract quantitative protein backbone information from experimental SDSL EPR data, accurate modeling methods are needed. For this purpose, we introduce chiLife, an open-source Python package for SDSL modeling designed to be extensible and integrable with other Python-based protein modeling packages. With chiLife, appropriate SDSL EPR experiments for protein model validation can be designed, and protein models can be refined using experimental SDSL EPR data as constraints.