Comparison of the penile microbiome in infant male circumcision: Mogen clamp versus Shangring.

BACKGROUND: This study aimed to characterise the infant penile (coronal sulcus) microbiome and the effects of early infant male circumcision (EIMC), following a standard surgical method (Mogen Clamp) and a non-surgical alternative (ShangRing). METHODS: We collected coronal sulcus swabs at baseline and on days 7 and 14 post-circumcision from infants assigned to receive EIMC by Mogen Clamp (n = 15) or ShangRing (n = 15), in a randomised trial in Rakai and Kakuuto, Uganda. We used 16S rRNA gene-based sequencing and broad-coverage qPCR to characterise the infant penile microbiome and assess the effects of EIMC in both study arms. FINDINGS: Prior to EIMC, the infant penile microbiome had a mixture of facultative and strict anaerobes. In both study arms, EIMC caused penile microbiome proportional abundance changes characterised by decreases in penile anaerobes [ShangRing Prevotella: -15.0%, (SD = 19.1); Mogen clamp Prevotella: -3.6% (11.2); ShangRing Veillonella: -11.3% (17.2); Mogen clamp Veillonella: -2.6% (11.8)] and increases in skin-associated facultative anaerobes [ShangRing Corynebacterium: 24.9%, (22.4); Mogen clamp Corynebacterium: 4.7% (21.3); ShangRing Staphylococcus: 21.1% (20.5); Mogen clamp Staphylococcus: 18.1% (20.1)]. Clostridium tetani was not detected during the study. INTERPRETATION: Mogen Clamp and ShangRing EIMC both changed the composition of the infant penile microbiome by reducing the proportional abundances of anaerobes and uropathogens, which is consistent with medical male circumcision findings in adults. C. tetani was not increased by either EIMC method. FUNDING: Bill and Melinda Gates Foundation.

Toward enhancement of antibody thermostability and affinity by computational design in the absence of antigen.

Over the past two decades, therapeutic antibodies have emerged as a rapidly expanding domain within the field of biologics. In silico tools that can streamline the process of antibody discovery and optimization are critical to support a pipeline that is growing more numerous and complex every year. High-quality structural information remains critical for the antibody optimization process, but antibody-antigen complex structures are often unavailable and in silico antibody docking methods are still unreliable. In this study, DeepAb, a deep learning model for predicting antibody Fv structure directly from sequence, was used in conjunction with single-point experimental deep mutational scanning (DMS) enrichment data to design 200 potentially optimized variants of an anti-hen egg lysozyme (HEL) antibody. We sought to determine whether DeepAb-designed variants containing combinations of beneficial mutations from the DMS exhibit enhanced thermostability and whether this optimization affected their developability profile. The 200 variants were produced through a robust high-throughput method and tested for thermal and colloidal stability (Tonset, Tm, Tagg), affinity (KD) relative to the parental antibody, and for developability parameters (nonspecific binding, aggregation propensity, self-association). Of the designed clones, 91% and 94% exhibited increased thermal and colloidal stability and affinity, respectively. Of these, 10% showed a significantly increased affinity for HEL (5- to 21-fold increase) and thermostability (>2.5C increase in Tm1), with most clones retaining the favorable developability profile of the parental antibody. Additional in silico tests suggest that these methods would enrich for binding affinity even without first collecting experimental DMS measurements. These data open the possibility of in silico antibody optimization without the need to predict the antibody-antigen interface, which is notoriously difficult in the absence of crystal structures.

PHAHST Potential: Modeling Sorption in a Dispersion-Dominated Environment.

PHAHST (potentials with high accuracy, high speed, and transferability) is a recently developed force field that utilizes exponential repulsion, multiple dispersion terms, explicit many-body polarization, and many-body van der Waals interactions. The result is a systematic approach to force field development that is computationally practical. Here, PHAHST is employed in the simulation for rare gas uptake of krypton and xenon in the metal-organic material, HKUST-1. This material has shown promise in use as an adsorptive separating agent and presents a challenge to model due to the presence of heterogeneous interaction sorption surfaces, which include pores with readily accessible, open-metal sites that compete with dispersion-dominated pores. Such environments are difficult to simulate with commonly used empirical force fields, such as the Lennard-Jones (LJ) potential, which perform better when electrostatics are dominant in determining the nature of sorption and alone are incapable of modeling interactions with open-metal sites. The effectiveness of PHAHST is compared to the LJ potential in a series of mixed Kr-Xe gas simulations. It has been demonstrated that PHAHST compares favorably with experimental results, and the LJ potential is inadequate. Overall, we establish that force fields with physically grounded repulsion/dispersion terms are required in order to accurately model sorption, as these interactions are an important component of the energy. Furthermore, it is shown that the simple mixing rules work nearly quantitatively for the true pair potentials, while they are not transferable for effective potentials like LJ.

Trailblazing Kr/Xe Separation: The Birth of the First Kr-Selective Material.

Efficient separation of Kr from Kr/Xe mixtures is pivotal in nuclear waste management and dark matter research. Thus far, scientists have encountered a formidable challenge: the absence of a material with the ability to selectively adsorb Kr over Xe at room temperature. This study presents a groundbreaking transformation of the renowned metal-organic framework (MOF) CuBTC, previously acknowledged for its Xe adsorption affinity, into an unparalleled Kr-selective adsorbent. This achievement stems from an innovative densification approach involving systematic compression of the MOF, where the crystal size, interparticle interaction, defects, and evacuation conditions are synergistically modulated. The resultant densified CuBTC phase exhibits exceptional mechanical resilience, radiation tolerance, and notably an unprecedented selectivity for Kr over Xe at room temperature. Simulation and experimental kinetic diffusion studies confirm reduced gas diffusion in the densified MOF, attributed to its small pore window and minimal interparticle voids. The lighter Kr element demonstrates facile surface passage and higher diffusivity within the material, while the heavier Xe encounters increased difficulty entering the material and lower diffusivity. This Kr-selective MOF not only represents a significant breakthrough in Kr separation but also demonstrates remarkable processability and scalability to kilogram levels. The findings presented herein underscore the transformative potential of engineered MOFs in addressing complex challenges, heralding a new era of Kr separation technologies.

Ethane/Ethylene Separations in Flexible Diamondoid Coordination Networks via an Ethane-Induced Gate-Opening Mechanism.

Separating ethane (C2H6) from ethylene (C2H4) is an essential and energy-intensive process in the chemical industry. Here, we report two flexible diamondoid coordination networks, X-dia-1-Ni and X-dia-1-Ni0.89Co0.11, that exhibit gate-opening between narrow-pore (NP) and large-pore (LP) phases for C2H6, but not for C2H4. X-dia-1-Ni0.89Co0.11 thereby exhibited a type F-IV isotherm at 273 K with no C2H6 uptake and a high uptake (111 cm3 g-1, 1 atm) for the NP and LP phases, respectively. Conversely, the LP phase exhibited a low uptake of C2H4 (12.2 cm3 g-1). This C2H6/C2H4 uptake ratio of 9.1 for X-dia-1-Ni0.89Co0.11 far surpassed those of previously reported physisorbents, many of which are C2H4-selective. In situ variable-pressure X-ray diffraction and modeling studies provided insight into the abrupt C2H6-induced structural NP to LP transformation. The promise of pure gas isotherms and, more generally, flexible coordination networks for gas separations was validated by dynamic breakthrough studies, which afforded high-purity (99.9%) C2H4 in one step.

Hydrogen bond unlocking-driven pore structure control for shifting multi-component gas separation function.

Purification of ethylene (C2H4) as the most extensive and output chemical, from complex multi-components is of great significance but highly challenging. Herein we demonstrate that precise pore structure tuning by controlling the network hydrogen bonds in two highly-related porous coordination networks can shift the efficient C2H4 separation function from C2H2/C2H4/C2H6 ternary mixture to CO2/C2H2/C2H4/C2H6 quaternary mixture system. Single-crystal X-ray diffraction revealed that the different amino groups on the triazolate ligands resulted in the change of the hydrogen bonding in the host network, which led to changes in the pore shape and pore chemistry. Gas adsorption isotherms, adsorption kinetics and gas-loaded crystal structure analysis indicated that the coordination network Zn-fa-atz (2) weakened the affinity for three C2 hydrocarbons synchronously including C2H4 but enhanced the CO2 adsorption due to the optimized CO2-host interaction and the faster CO2 diffusion, leading to effective C2H4 production from the CO2/C2H2/C2H4/C2H6 mixture in one step based on the experimental and simulated breakthrough data. Moreover, it can be shaped into spherical pellets with maintained porosity and separation performance.

Addressing chronic pain disparities between Black and White people: a narrative review of socio-ecological determinants.

A 2019 review article modified the socio-ecological model to contextualize pain disparities among different ethnoracial groups; however, the broad scope of this 2019 review necessitates deeper socio-ecological inspection of pain within each ethnoracial group. In this narrative review, we expanded upon this 2019 article by adopting inclusion criteria that would capture a more nuanced spectrum of socio-ecological findings on chronic pain within the Black community. Our search yielded a large, rich body of literature composed of 174 articles that shed further socio-ecological light on how chronic pain within the Black community is influenced by implicit bias among providers, psychological and physical comorbidities, experiences of societal and institutional racism and biomedical distrust, and the interplay among these factors. Moving forward, research and public-policy development must carefully take into account these socio-ecological factors before scaling up pre-existing solutions with questionable benefit for the chronic pain needs of Black individuals.

An aliphatic MOF with a molecular sieving effect for efficient C2H2/C2H4 separation.

A metal-organic framework, SDMOF-1, with rigid pores of about 3.4 Å, which is appropriate for accommodating C2H2 molecules, exhibits high C2H2 adsorption capacity and great separation capability of the C2H2/C2H4 mixture. This work provides a new method to design aliphatic MOFs with a molecular sieving effect to realize efficient gas separation.

Bioinspired Design of a Giant [Mn86 ] Nanocage-Based Metal-Organic Framework with Specific CO2 Binding Pockets for Highly Selective CO2 Separation.

Adsorption-based removal of carbon dioxide (CO2 ) from gas mixtures has demonstrated great potential for solving energy security and environmental sustainability challenges. However, due to similar physicochemical properties between CO2 and other gases as well as the co-adsorption behavior, the selectivity of CO2 is severely limited in currently reported CO2 -selective sorbents. To address the challenge, we create a bioinspired design strategy and report a robust, microporous metal-organic framework (MOF) with unprecedented [Mn86 ] nanocages. Attributed to the existence of unique enzyme-like confined pockets, strong coordination interactions and dipole-dipole interactions are generated for CO2 molecules, resulting in only CO2 molecules fitting in the pocket while other gas molecules are prohibited. Thus, this MOF can selectively remove CO2 from various gas mixtures and show record-high selectivities of CO2 /CH4 and CO2 /N2 mixtures. Highly efficient CO2 /C2 H2 , CO2 /CH4 , and CO2 /N2 separations are achieved, as verified by experimental breakthrough tests. This work paves a new avenue for the fabrication of adsorbents with high CO2 selectivity and provides important guidance for designing highly effective adsorbents for gas separation.

Ideals of counseling practice: Therapeutic insights from an Indigenous first nations-controlled treatment program.

Indigenous Canadians suffer disproportionately from mental health concerns tied to histories of colonization, including exposure to Indian Residential Schools. Previous research has indicated that preferred therapies for Indigenous populations fuse traditional cultural practices with mainstream treatment. The present study comprised 32 interviews conducted with Indigenous administrators, staff, and clients at a reserve-based addiction treatment center to identify community-driven and practical therapeutic solutions for remedying histories of coercive colonial assimilation. Thematic analysis of semi-structured interviews revealed that counselors tailored therapy through cultural preferences, including the use of nonverbal expression, culturally appropriate guidance, and alternative delivery formats. Additionally, they augmented mainstream therapeutic activities with Indigenous practices, including the integration of Indigenous concepts, traditional practices, and ceremonial activities. Collectively, this integration of familiar counseling approaches and Indigenous cultural practices in response to community priorities resulted in an innovative instance of therapeutic fusion that may be instructive for cultural adaptation efforts in mental health treatment for Indigenous populations and beyond. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Design and validation of Dolosigranulum pigrum specific PCR primers using the bacterial core genome.

Dolosigranulum pigrum-a lactic acid bacterium that is increasingly recognized as an important member of the nasal microbiome. Currently, there are limited rapid and low-cost options for confirming D. pigrum isolates and detecting D. pigrum in clinical specimens. Here we describe the design and validation of a novel PCR assay targeting D. pigrum that is both sensitive and specific. We designed a PCR assay targeting murJ, a single-copy core species gene identified through the analysis of 21 D. pigrum whole genome sequences. The assay achieved 100% sensitivity and 100% specificity against D. pigrum and diverse bacterial isolates and an overall 91.1% sensitivity and 100% specificity using nasal swabs, detecting D. pigrum at a threshold of 1.0 × 104 D. pigrum 16S rRNA gene copies per swab. This assay adds a reliable and rapid D. pigrum detection tool to the microbiome researcher toolkit investigating the role of generalist and specialist bacteria in the nasal environment.

Behavioral health services in Urban American Indian Health Programs: Results from six site visits.

This study explores behavioral health services for American Indians and Alaska Natives (AIANs) at six Urban Indian Health Programs (UIHPs). Interviews and focus groups with clinicians and staff inquired about behavioral health treatment available, service needs, client population, and financial and staffing challenges. Resulting site profiles were created based on focused coding and integrative memoing of site visit field notes and respondent transcripts. These six UIHPs evidenced diversity across multiple facets of service delivery even as they were united in their missions to provide accessible and effective behavioral health treatment to urban AIAN clients. Primary challenges to service provision included heterogenous client populations, low insurance coverage, limited provider knowledge, lack of resources, and incorporation of traditional healing. Collaborative research with UIHPs harbors the potential to recognize challenges, identify solutions, and share best practices across this crucial network of health care sites for improving urban AIAN well-being.

Clinical and economic burden of benign and malignant skin lesions in renal transplant recipients.

BACKGROUND: Studies evaluating the economic burden of dermatological care in the transplant setting are currently not available in Australia. AIMS: To evaluate the clinical and economic burden of benign and malignant skin lesions in renal transplant recipients in Central Queensland. METHODS: A bottom-up approach was used to determine the clinical burden and direct costs from patient-level Medicare data obtained from Service Australia for skin lesions. RESULTS: Seventy-six percent of the renal transplant population in Central Queensland participated in this study. The median age was 57.0 years (standard deviation ± 13.6) and the majority (61.8%) of participants were men. The mean duration after transplant surgery was 99.9 months (interquartile range, 73.2-126.6 months). During a 2-year follow-up, 22 (40%) patients were diagnosed with benign skin lesions, 21 (38%) with nonmelanoma skin carcinoma (NMSC) and one (2%) with melanoma. There was a total of 231 visits to clinicians for diagnostic and therapeutic skin procedures and the direct costs to Medicare was $48 806 Australian Dollars (AUD) or $30 427 US Dollars (USD). Approximately 86% of the total direct costs was spent for nonNMSC and mean direct costs for NMSC was $763 AUD (or $476 USD). CONCLUSION: This Medicare data-based study provides further insight into the burgeoning clinical and economic burden of the care for benign and malignant skin lesions in the renal transplantation setting in Australia.

Highly Robust Microporous Metal-Organic Frameworks for Efficient Ethylene Purification under Dry and Humid Conditions.

Two C2 H6 -selective metal-organic framework (MOF) adsorbents with ultrahigh stability, high surface areas, and suitable pore size have been designed and synthesized for one-step separation of ethane/ethylene (C2 H6 /C2 H4 ) under humid conditions to produce polymer-grade pure C2 H4 . Experimental results reveal that these two MOFs not only adsorb a high amount of C2 H6 but also display good C2 H6 /C2 H4 selectivity verified by fixed bed column breakthrough experiments. Most importantly, the good water stability and hydrophobic pore environments make these two MOFs capable of efficiently separating C2 H6 /C2 H4 under humid conditions, exhibiting the benchmark performance among all reported adsorbents for separation of C2 H6 /C2 H4 under humid conditions. Moreover, the affinity sites and their static adsorption energies were successfully revealed by single crystal data and computation studies. Adsorbents described in this work can be used to address major chemical industrial challenges.

Culturally Adapting Mind-Body Interventions for Black Individuals with Chronic Pain: Arguments and Recommendations Towards a Task-Sharing Approach.

Compared to non-Hispanic White individuals, non-Hispanic Black Individuals report worse chronic pain from a variety of medical issues. Among the options for non-pharmacological pain treatment, mind-body interventions (MBI) are a promising modality to help Black individuals manage their chronic pain effectively. MBIs such as mindfulness meditation improve chronic pain and chronic pain-related outcomes by shifting the individual's perception of pain away from stress-related cognitive appraisals, emotional reactions, and behaviors. MBIs may also address disparities in chronic pain outcomes between Black and White individuals because of their contextual overlap with (1) centering and contemplative prayer, (2) racial empowerment, and (3) social support. Despite this overlap, the demand for MBIs among Black individuals has generally been low due to lingering access and acceptability barriers. To reduce these barriers for Black individuals with chronic pain, we must adopt a community-engaged approach and culturally adapt MBIs for the specific historic, environmental, financial, and psychosocial needs of Black individuals. Example adaptations include increasing Black representation among MBI instructors, reducing geographical access barriers, accommodating the financial and personal realities of Black adults, and explicitly allowing relevant attitudes, practices, and terms.

Significantly Enhanced Carbon Dioxide Selective Adsorption via Gradual Acylamide Truncation in MOFs: Experimental and Theoretical Research.

A gradual amide truncation strategy was presented to tune the pore chemistry and CO2 capture performance of a series of tetracarboxylate-based Cu-MOFs. These MOFs exhibited a high density of Lewis basic sites (LBSs) and open metal sites and were prepared with the goal to enhance CO2 selective adsorption capacity. [Cu2(L1)(H2O)2]n (NJU-Bai42: NJU-Bai for Nanjing University Bai's group), [Cu2(L2) (H2O)2]n (NJU-Bai17), and [Cu2(L3)(H2O)2]n (NTUniv-60: NTUniv for Nantong University) were synthesized, and we observed that the CO2 adsorption capacities and MOF structures were impacted by subtle changes in ligands. Interestingly, although the NTUniv-60 was decorated with the least LBSs in these three MOFs, its CO2 adsorption capacity reached 270 (53.0 wt %) and 164 (32.2 wt %) cm3 g-1 at 273 and 296 K under 1 bar, respectively, which is the highest data reported for MOFs under similar conditions. From the grand canonical Monte Carlo (GCMC) simulation, the cooperative interactions between the CO2 molecules within the shuttle-shaped cages of NTUniv-60 could potentially explain why the CO2 uptake is high in this material.

Epidermal Growth Factor Receptor Inhibitor Treatment Timing does not Impact Survival in Stage 4 Colon Cancer Treatment: A Retrospective Study.

Introduction: Colon cancer impacts the lives of Kansans and those across the United States. Epidermal growth factor receptor (EGFR) inhibitors, such as panitumumab and cetuximab, have gained popularity as first-line treatment for stage 4 colon cancer despite their toxicities and have been used by clinicians in later lines of therapy. EGFR inhibitors have been proven to be an efficacious first-line treatment for stage 4 colon cancer, but no study has investigated outcomes comparing EGFR inhibitors as first-line treatment to its use as second- or third-line treatment. This study investigated EGFR inhibitor therapy estimated overall survival when used as first-, second-, and third-line treatment for stage 4 colon cancer. Methods: A retrospective review was done for patients with stage 4 colon cancer who underwent EGFR inhibitor treatment at a large academic center from November 2007 to August 2021. The patients were stratified into five groups by the line in which they received the EGFR inhibitor treatment. A log-rank test was used to analyze the groups, and the median survival for each group was determined. Results: A total of 68 patients were reviewed; 18 received first-line, 23 received second-line, 18 received third-line, 6 received fourth-line, and 3 received sixth-line treatment with an EGFR inhibitor. Fourth- and sixth-line therapies were excluded due to small patient size. There was no significant difference in estimated survival time between any of the lines. Median survival of the therapies was found. Conclusions: There was no statistical difference in survival between the first-, second-, or third-line groups, which may provide justification for its use as a second- or third-line therapy.

Psychosocial Predictors of Chronic Musculoskeletal Pain Outcomes and their Contextual Determinants Among Black Individuals: A Narrative Review.

Black communities are disproportionally affected by Chronic Musculoskeletal Pain (CMP), but little is known about the psychological predictors of CMP outcomes and their contextual determinants among Black individuals. To address this gap, we conducted a narrative review of extant literature to (1) report the major conceptual models mentioned in prior work explaining the link between contextual determinants and psychological responses to pain among Black individuals with CMP; and (2) describe psychological factors related to CMP outcomes in this population that are highlighted in the literature. We searched 4 databases (APA PsycNet, PubMed/MEDLINE, Scopus, and Google Scholar) using the following search terms: musculoskeletal pain, chronic pain, mental health, psychological, coping, health disparities, contextual factors, conceptual models, psychosocial, Black, African American, pain, disability, and outcomes. We illustrate 3 relevant conceptual models - socioecological, cumulative stress, and biopsychosocial - related to contextual determinants and several psychological factors that influence CMP outcomes among Black individuals: (1) disproportionate burden of mental health and psychiatric diagnoses, (2) distinct coping strategies, (3) pain-related perceived injustice and perceived racial/ethnic discrimination, and (4) preferences and expectations related to seeking and receiving pain care. The detailed clinical and research implications could serve as a blueprint for the providers and clinical researchers to address health disparities and improve care for Black individuals with CMP. PERSPECTIVE: This narrative review illustrates conceptual models explaining the link between contextual determinants and psychological responses to pain among Black individuals with chronic musculoskeletal pain. We discuss 3 relevant conceptual models - socioecological, cumulative stress, biopsychosocial -, and 4 psychological factors: disproportionate burden of mental health, distinct coping strategies, perceived injustice/discrimination, preferences/expectations.