bluuebunny/crossref_metadata_2025 huggingface dataset:
Atheism in history
Authors: Baggini Julian
Published: August 2021

‘Atheism in history’ traces the origins and history of atheism. Atheism has its origins in Ancient Greece and although there have always been people who did not believe in God, atheism did not emerge as an overt and avowed belief system until late in the Enlightenment. Since the Enlightenment, almost all atheists have advocated state secularism, which has been one of the great triumphs of Western civilization. It is important to remember, however, that the history of Western atheism is not the history of global atheism. Despite the growth of atheism, suspicion, and even fear, of atheists remains widespread.
Climate surprises
Authors: Maslin Mark
Published: August 2021

‘Climate surprises’ assesses the possibility that there are thresholds or tipping points in the climate system that may occur as we warm the planet. Scientists have been concerned about these tipping points over the last three decades. One can examine the way different parts of the climate system respond to climate change with four scenarios. These include linear but delayed response; muted or limited response; delayed and non-linear response; and threshold response. It is worth considering here the melting of the Greenland and/or Western Antarctic ice sheet; the slowing down of the North Atlantic deep ocean circulation; the potential massive release of methane from melting gas hydrates; and the possibility of the Amazon rainforest dieback.
In vitro ictogenesis is stochastic at the single neuron level
Authors: Lau Lauren A , Staley Kevin J , Lillis Kyle P
Published: August 2021

Seizure initiation is the least understood and most disabling element of epilepsy. Studies of ictogenesis require high speed recordings at cellular resolution in the area of seizure onset. However, in vivo seizure onset areas cannot be determined at the level of resolution necessary to enable such studies.

To circumvent these challenges, we used novel GCaMP7-based calcium imaging in the organotypic hippocampal slice culture model of post-traumatic epilepsy in mice. Organotypic hippocampal slice cultures generate spontaneous, recurrent seizures in a preparation in which it is feasible to image the activity of the entire network (with no unseen inputs existing). Chronic calcium imaging of the entire hippocampal network, with paired electrophysiology, revealed three patterns of seizure onset: (i) low amplitude fast activity; (ii) sentinel spike; and (iii) spike burst and low amplitude fast activity onset. These patterns recapitulate common features of human seizure onset, including low voltage fast activity and spike discharges. Weeks-long imaging of seizure activity showed a characteristic evolution in onset type and a refinement of the seizure onset zone. Longitudinal tracking of individual neurons revealed that seizure onset is stochastic at the single neuron level, suggesting that seizure initiation activates neurons in non-stereotyped sequences seizure to seizure.

This study demonstrates for the first time that transitions to seizure are not initiated by a small number of neuronal ‘bad actors’ (such as overly connected hub cells), but rather by network changes which enable the onset of pathology among large populations of neurons.
Androgen receptor polymorphism, testosterone levels, and prognosis in patients with acute myocardial infarction
Authors: Wang Anne , Flanagan John , Arver Stefan , Norhammar Anna , Näsman Per , Rydén Lars , Mellbin Linda G
Published: August 2021

Aims

Low testosterone has been associated with cardiovascular disease in men but with contradictory findings. Testosterone bind to the androgen receptor and polymorphisms of the receptor gene such as CAG repeat length may affect transcriptional activity, possibly mitigating testosterone effects. The aims were to study the CAG repeat length and testosterone levels at four time points following a myocardial infarction (MI) and to analyse possible relationships between CAG repeat length and cardiovascular prognosis.

Methods and results

Male patients admitted for acute MI (n = 122) from the Glucose in Acute Myocardial Infarction study were included. Blood samples were drawn at four time points (day after admission, at discharge, and at 3 and 12 months post-infarction) for assessment of testosterone levels. Patients were followed for a median of 11.6 years. Cox regression analyses were performed for CAG repeat length by one unit increment and by > vs. ≤median for cardiovascular events and all-cause mortality. Median CAG repeat length was 20. There was no difference in testosterone levels at each time point when dividing the cohort into ≤ vs. >CAG repeat median (=20). There was no association between CAG repeat length either as a continuous or categorical variable in unadjusted and age-adjusted Cox analyses for cardiovascular events. While CAG >20 was associated with all-cause mortality in unadjusted analyses (hazard ratio 2.19, 95% confidence interval 1.13–4.22; P = 0.02), it did not remain significant following adjustment for age.

Conclusion

CAG repeat length was not associated with testosterone levels or prognosis in men with acute MI.
Taxonomic Uncertainty and the Anomaly Zone: Phylogenomics Disentangle a Rapid Radiation to Resolve Contentious Species (Gila robustaComplex) in the Colorado River
Authors: Chafin Tyler K , Douglas Marlis R , Bangs Max R , Martin Bradley T , Mussmann Steven M , Douglas Michael E
Published: August 2021

Species are indisputable units for biodiversity conservation, yet their delimitation is fraught with both conceptual and methodological difficulties. A classic example is the taxonomic controversy surrounding the Gila robusta complex in the lower Colorado River of southwestern North America. Nominal species designations were originally defined according to weakly diagnostic morphological differences, but these conflicted with subsequent genetic analyses. Given this ambiguity, the complex was re-defined as a single polytypic unit, with the proposed “threatened” status under the U.S. Endangered Species Act of two elements being withdrawn. Here we re-evaluated the status of the complex by utilizing dense spatial and genomic sampling (n = 387 and >22 k loci), coupled with SNP-based coalescent and polymorphism-aware phylogenetic models. In doing so, we found that all three species were indeed supported as evolutionarily independent lineages, despite widespread phylogenetic discordance. To juxtapose this discrepancy with previous studies, we first categorized those evolutionary mechanisms driving discordance, then tested (and subsequently rejected) prior hypotheses which argued phylogenetic discord in the complex was driven by the hybrid origin of Gila nigra. The inconsistent patterns of diversity we found within G. robusta were instead associated with rapid Plio-Pleistocene drainage evolution, with subsequent divergence within the “anomaly zone” of tree space producing ambiguities that served to confound prior studies. Our results not only support the resurrection of the three species as distinct entities but also offer an empirical example of how phylogenetic discordance can be categorized within other recalcitrant taxa, particularly when variation is primarily partitioned at the species level.
Oral tolerance as antigen-specific immunotherapy
Authors: Pinheiro-Rosa Natália , Torres Lícia , Oliveira Mariana de Almeida , Andrade-Oliveira Marcos Felipe , Guimarães Mauro Andrade de Freitas , Coelho Monique Macedo , Alves Juliana de Lima , Maioli Tatiani Uceli , Faria Ana M Caetano
Published: August 2021

Oral tolerance is a physiological phenomenon described more than a century ago as a suppressive immune response to antigens that gain access to the body by the oral route. It is a robust and long-lasting event with local and systemic effects in which the generation of mucosally induced regulatory T cells (iTreg) plays an essential role. The idea of using oral tolerance to inhibit autoimmune and allergic diseases by oral administration of target antigens was an important development that was successfully tested in 1980s. Since then, several studies have shown that feeding specific antigens can be used to prevent and control chronic inflammatory diseases in both animal models and clinically. Therefore, oral tolerance can be classified as an antigen-specific form of oral immunotherapy (OIT). In the light of novel findings on mechanisms, sites of induction and factors affecting oral tolerance, this review will focus on specific characteristics of oral tolerance induction and how they impact in its therapeutic application.
Influence of Imaging Features and Technique on US-guided Tattoo Ink Marking of Axillary Lymph Nodes Removed at Sentinel Lymph Node Biopsy in Women With Breast Cancer
Authors: Pajcini Marlen , Wapnir Irene , Tsai Jacqueline , Edquilang Joanne , DeMartini Wendy , Ikeda Debra
Published: August 2021

Objective

To describe tattoo ink marking of axillary lymph nodes (TIMAN) and the elements leading to successful removal at sentinel lymph node biopsy (SLNB).

Methods

An IRB-approved retrospective image review was conducted of breast cancer patients who underwent SLNB after TIMAN from February 2013 to August 2017, noting patient and tattooed lymph node (TLN) features, initial biopsy type, time to surgery, if the TLN was identified at surgery, and correlation with the SLN. Cases were divided into two groups: the presurgical group, which had primary surgery, and the pre-neoadjuvant chemotherapy (NACT) group, which underwent surgery after completing NACT.

Results

Of 30 patients who underwent 32 TIMAN procedures, 10 (33.3%) were presurgical and 20 (66.7%) were pre-NACT. The average lymph node (LN) depth from the skin was 1.6 cm, with an average of 0.3 mL of tattoo ink injected. Of 32 procedures, 29 (90.6%) had US images demonstrating the injection. Of these, 10 (34.5%) were injected in the LN cortex surface and 19 (65.5%) in the middle cortex. Seven (24.1%) were injected in the LN lateral aspect, 12 (41.4%) in the mid aspect, and 10 (34.5%) in the medial aspect. Of 32 LNs, 28 (87.5%) were tattooed immediately after initial biopsy and 4 (12.5%) at a later date. At SLNB, all 32 (100%) TLNs were identified, all correlated with the SLN, and 10 (31.3%) were positive for cancer.

Conclusion

Using an average of 0.3 mL of tattoo ink, all TLNs were successfully identified for removal at surgery, despite variability in LN and injection factors.
The Threshold-Crossing Effect: Just-Below Pricing Discourages Consumers to Upgrade
Authors: Kim Junha , Malkoc Selin A , Goodman Joseph K
Published: August 2021

Managers often set prices just-below a round number (e.g., $39)—a strategy that lowers price perceptions and increases sales. The authors question this conventional wisdom in a common consumer context: upgrade decisions (e.g., whether to upgrade a rental car or hotel room). Seven studies—including one field study—provide empirical evidence for a threshold-crossing effect. When a base product is priced at or just-above a threshold, consumers are more likely to upgrade and spend more money (studies 1–3) because they perceive the upgrade option as less expensive (study 4), and they place less weight on price (study 5). Testing theoretically motivated and managerially relevant boundary conditions, studies find that the threshold-crossing effect is mitigated under sequential choice (study 6) and when an upgrade price crosses an upper threshold (study 7). These studies demonstrate that a small increase in price on a base product can decrease price perceptions of an upgrade option and, thus, increase consumers’ likelihood to upgrade. Results suggest that just-below pricing, while sometimes advantageous at first, may not always be an optimal strategy for managers trying to encourage consumers to ultimately choose an upgrade option.
Short-term outcomes following mini-open repair of chronic gluteus medius tendon tears using a double-row technique
Authors: Uso Marc Barrera , Bothorel Hugo , Poultsides Lazaros , Christofilopoulos Panayiotis
Published: August 2021

Gluteal tendon tears represent a common but underreported cause of lateral hip pain and dysfunction. In case of conservative management failure, a surgical procedure must be performed to relieve patient symptoms. Current operative treatments, either open or endoscopic, have been however associated with different drawbacks which led to the introduction of the mini-open technique. The aim of this study was to evaluate and report the short-term outcomes of patients operated through the aforementioned surgical technique for gluteus medius (GM) chronic tears. We retrospectively analysed the records of 14 consecutive patients operated at the La Tour hospital by mini-open repair using a double-row technique for full-thickness GM chronic tears. Intra- and post-operative complications were recorded. The pre- and post-operative pain on visual analogue scale (pVAS), modified Harris Hip score (mHHS), abduction strength and gait dysfunction were assessed for all patients. Pre- and post-operative values were compared to evaluate whether improvements were statistically significant and clinically relevant. The study cohort comprised 13 women (93%) and 1 man (3%) aged 62.4 ± 18.0 at index surgery. No intra- or post-operative complications were noted. Compared to pre-operative values, patients reported a significant improvement in mHHS (59.1 ± 7.1 vs 92.7 ± 4.6) and pVAS (7.4 ± 1.0 vs 1.3 ± 1.3) at last follow-up. Patients exhibited a perfect improvement in muscle strength (3.6 ± 0.5 vs 5.0 ± 0.0), and the proportion of patients with a positive Trendelenburg sign decreased from 71% to 0%. Mini-open repair of chronic GM tendon tears using a double-row technique demonstrated excellent clinical and functional outcomes at short follow-up.

Level of Evidence IV.
Neutral responses of plant community Ca concentration to nitrogen enrichment in a semiarid grassland
Authors: Hou Shuang-Li , Lü Xiao-Tao , Yang Jun-Jie
Published: August 2021

Calcium (Ca) is an essential nutrient for plant growth and Ca concentrations in forage have important implications for ruminant diet and health. It remains an open question whether forage Ca concentration would be decreased by increasing nitrogen (N) deposition. We manipulated the increasing rates of N addition (2008–2015) in a semiarid grassland, northern China. Plant Ca concentrations for all species were examined in each plot under N treatment. The Ca concentrations at functional group and community levels were calculated based on the concentration of each species presented and their relative biomass in each plot. We found that community-level Ca concentration remained stable across a gradient of wide-ranged N addition rates, although Ca concentration at both species and functional group levels showed negative responses to N enrichment. Given that forbs had higher Ca concentration than grasses, the increasing relative biomass of forbs canceled out the negative responses of species-level and functional group-level Ca concentration. Our results further showed that community Ca pool showed a positive but saturating response to N addition, with a threshold at the rate of 10 g N m−2 yr−1. Our findings highlight the role of changes in plant relative biomass in controlling the responses of forage Ca concentration and stock to N enrichment.
Explaining variation in productivity requires intraspecific variability in plant height among communities
Authors: Zhang Li , Liu Xiang , Zhou Shurong , Shipley Bill
Published: August 2021

While recent studies have shown the importance of intraspecific trait variation in the processes of community assembly, we still know little about the contributions of intraspecific trait variability to ecosystem functions. Here, we conducted a functional group removal experiment in an alpine meadow in Qinghai-Tibetan Plateau over 4 years to investigate the relative importance of inter- and intraspecific variability in plant height for productivity. We split total variability in plant height within each of 75 manipulated communities into interspecific variability (TVinter) and intraspecific variability within a community (ITVwithin). Community-weighted mean height among communities was decomposed into fixed community-weighted mean (CWMfixed) and intraspecific variability among communities (ITVamong). We constructed a series of generalized additive mixed models and piecewise structural equation modeling to determine how trait variability (i.e. TVinter, ITVwithin, CWMfixed and ITVamong) indirectly mediated the changes in productivity in response to functional group removal. Community productivity was not only affected directly by treatment manipulations, but also increased with both inter- and intraspecific variability (i.e. CWMfixed and ITVamong) in plant height indirectly. This suggests that both the ‘selection effect’ and a ‘shade-avoidance syndrome’ can incur higher CWMfixed and ITVamong, and may simultaneously operate to regulate productivity. Our findings provide new evidence that, besides interspecific variability, intraspecific trait variability in plant height also plays a role in maintaining net primary productivity.
Avelumab in newly diagnosed glioblastoma
Authors: Jacques Francois H , Nicholas Garth , Lorimer Ian A J , Sikati Foko Victorine , Prevost Jasmine , Dumais Nathalie , Milne Katy , Nelson Brad H , Woulfe John , Jansen Gerard , Apedaile B Erik
Published: August 2021

Background

Glioblastoma (GBM) is known to use both local and systemic immunosuppressive strategies. One such strategy is the expression of the immune checkpoint protein programmed cell death ligand-1 (PD-L1) by both tumor cells and tumor-associated immune cells. Recent phase III trials using IgG4 antibodies targeting PD-1, the ligand for PD-L1, failed to show any benefit. Avelumab is an IgG1 monoclonal antibody targeting PD-L1. In contrast to the previously tested immune checkpoint inhibitors, it can directly bind tumor cells and immune cells expressing PD-L1 and can induce antibody-dependent cellular cytotoxicity.

Methods

We conducted a single center, open label, phase II study where avelumab 10 mg/kg IV Q2W was added concurrently to the first monthly temozolomide cycle in patients with newly diagnosed GBM. Immunohistochemical analyses were performed on surgery samples. The primary objective was safety. Secondary objectives were efficacy outcomes according to the immunotherapy Response Assessment in Neuro Oncology criteria, progression free survival (PFS), and overall survival (OS). Exploratory objectives aimed at determining prognostic biomarkers.

Results

Thirty patients were started on therapy and two were lost to follow-up. Median follow-up time (reverse Kaplan-Meier) was 41.7 months (IQR: 28.3–43.4). Three (10.0%) patients had a related or possibly related treatment emergent adverse event that lead to transient or permanent discontinuation of avelumab. Eight (26.7%) patients had one or more immune-related adverse events, and 8 (26.7%) patients had an infusion-related reaction. The overall response rate was 23.3%, median PFS was 9.7 months, and the median OS was 15.3 months. No pretreatment biomarkers showed any predictive value.

Conclusions

The addition of avelumab to standard therapy in patients with GBM was not associated with any new safety signal. There was no apparent improvement in OS.

Trial Registration

NCT03047473 Registered February 9, 2017.
Hypoglossal Nerve Schwannoma With Severe Brainstem Compression: Microsurgical Excision by Extreme Lateral Approach: 2-Dimensional Operative Video
Authors: Zeeshan Qazi , Balasubramanian Sneha Chitra , Carrasco Hernandez Juan P , Shenoy Varadaraya S , Abecassis Isaac Josh , Sekhar Laligam N
Published: August 2021

A 37-yr-old male presented with a history of left-sided tongue atrophy and fasciculations and weakness of upper limbs for 3 mo. Magnetic resonance imaging (MRI) revealed a large, partially cystic tumor with severe compression of the brainstem and spinal cord, with expansion and erosion of the hypoglossal canal. Computed tomography (CT) angiography showed the left vertebral artery to be anteriorly displaced by the tumor.

 A retrosigmoid craniotomy and craniectomy were performed followed by mastoidectomy with unroofing the posterior aspect of the sigmoid sinus. The foramen magnum was completely unroofed. The hypoglossal canal was exposed with a diamond drill and an ultrasonic bone curette, and a tumor was seen within the expanded canal. C1 lamina was removed partially in the lateral aspect, and the occipital condyle was partially removed. After opening the dura mater, the tumor was found to be stretching the eleventh cranial nerve. The tumor was debulked, and dissected from the cranial nerve fibers. The vertebral artery, anterior spinal artery, and other branches displaced by the tumor were carefully preserved. The tumor was removed from the hypoglossal canal with a curette. The patient recovered well, with the resolution of his upper limb weakness. Patient modified Rankin Scale was 1 at 6-mo follow-up. The postoperative MRI showed a small remnant inside the hypoglossal canal, and it was treated by radiosurgery.

 This 2-dimensional video demonstrates the technique of complete microsurgical removal of a complex tumor with preservation of cranial nerves and vertebral artery.

 Informed consent was obtained from the patient prior to the surgery, which included videotaping of the procedure and its distribution for educational purposes. Also, all relevant patient identifiers have been removed from the video and accompanying radiology slides.
Completion Posterior Quadrant Disconnection After Failed Temporal Lobectomy: 2-Dimensional Operative Video
Authors: Patel Saarang , Markosian Christopher , Dominguez Jose F , Taha Firas A , Tomycz Luke D
Published: August 2021

Epilepsy is a chronic seizure disorder that affects about 1% of the global population.
1
When seizure freedom cannot be obtained solely through antiseizure medicines (ASMs), the condition is termed medically refractory epilepsy (MRE).
2,3
Though posterior quadrant disconnection (PQD) is underutilized in our experience, it is a highly effective surgical procedure for MRE restricted to the temporal, parietal, and/or occipital lobes.
4-12
In this operative video, we demonstrate a right-sided completion PQD following failed temporal lobectomy in an 8-yr-old female with focal MRE. We review technical nuances, including (1) extension/revision of prior scalp incision, (2) placement of subdural strip for the identification of phase reversal and central sulcus, (3) disconnection of parietal and occipital lobes, (4) extension of the corticectomy to the pia overlying the falcotentorial junction and into the prior temporal lobectomy defect, and (5) posterior disconnection of the corpus callosum. Postoperatively, the patient experienced subtle left-arm weakness and central fever, both of which resolved. An external ventricular drain (EVD) was placed in the ventricle/operative cavity and left for 3 to 4 d until the draining cerebrospinal fluid (CSF) cleared. As of 3-mo follow-up, she has been seizure-free without complications. In summary, PQD is a safe and effective treatment option for MRE that can be utilized not only as an initial operation but also after failed surgery.

 Appropriate patient consent was obtained to perform this procedure and present this clinical case and surgical video for academic purposes.

 Image at 4:00 licensed under CC BY-2.5, 2006, modified from http://upload.wikimedia.org/wikipedia/commons/7/70/Lateral_head_skull.jpg (flipped and rotated). Image at 4:42, Public Domain: Gray H. Anatomy of the Human Body. 1918. Bartleby.com, https://commons.wikimedia.org/wiki/File:Lobes_of_the_brain_NL.svg; flipped, modified. Image at 6:42, Public Domain: House EL, Pansky B. A Functional Approach to Neuroanatomy. 1960. McGraw-Hill Book Company; https://upload.wikimedia.wikipedia.commons/5/52/Lawrence_1960_2.3.png; modified.
High-Quality Complete Genome Resource of Tomato Rhizosphere StrainPseudomonas donghuensisP482, a Representative of a Species with Biocontrol Activity Against Plant Pathogens
Authors: Krzyżanowska Dorota M. , Iwanicki Adam , Czajkowski Robert , Jafra Sylwia
Published: August 2021

Strain P482 was isolated from a tomato rhizosphere and classified as Pseudomonas donghuensis. The P. donghuensis species was first established in 2015 and currently consists of only four strains: P482, HYST, SVBP6, and 22G5. P. donghuensis strains antagonize plant pathogens, including bacteria, fungi, and oomycetes, and, therefore, are of high interest regarding their biological control potential to combat plant diseases. The antimicrobial activity of P. donghuensis P482 is based on the production of iron-scavenging compound 7-hydroxytropolone, antifungal volatile organic compounds, and as-yet-unidentified secondary metabolites. Here, we report a complete genome resource for P. donghuensis strain P482. The genome consists of a single chromosome (5,656,185 bp) with 5,258 open reading frames (5,158 protein-coding genes, 74 transfer RNAs, 22 ribosomal RNAs, 3 noncoding RNAs, and 1 transfer-messenger RNA) and no plasmid. We believe that information on the first high-quality, complete genome of P. donghuensis will provide resources for analyses targeting the biological control potential of this species and understanding the traits essential for plant–microbe interaction.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
From Roots to Leaves: The Capacity of Micromonospora to Colonize Different Legume Tissues
Authors: Benito Patricia , Carro Lorena , Bacigalupe Rodrigo , Ortúzar Maite , Trujillo Martha E.
Published: August 2021

An important number of Micromonospora strains have been reported from nitrogen-fixing root nodules of legume and actinorhizal plants. However, the question of whether this bacterium can also be found in other parts of these plants remains unanswered. More than 150 strains were recovered from different Lupinus angustifolius and Pisum sativum tissues, including leaves, stems, roots, and nodules. In all, 97% of the isolates were identified by 16S ribosomal RNA gene sequence in the target genus and were associated with 27 different Micromonospora spp. Plant-polymer-degrading enzymes are suspected to play a role in the colonization of plants. To this end, bacterial enzymatic activity assays for amylases, cellulases, chitinases, pectinases, and xylanases were determined. All strains produced xylanases and pectinases, while 98.6, 98, and 94.6% of them produced amylases, cellulases, and chitinases, respectively. The most productive strains included seven isolates from P. sativum and one from L. angustifolius. Strain Micromonospora lupini ML01-gfp was used to determine its capacity to reach and colonize different plant organs using P. sativum as the plant model. Stem and leaf samples were monitored by optical and fluorescence microscopy to locate the tagged strain. These results strongly suggest that Micromonospora is able not only to infect nitrogen-fixing nodules but also to reach other parts of the host plant, especially the leaves.
Cervical Cancer Risk and Screening Among Women Seeking Assistance With Basic Needs
Authors: Kuroki Lindsay M. , Massad L. Stewart , Woolfolk Candice , Thompson Tess , McQueen Amy , Kreuter Matthew W.
Published: August 2021

(Abstracted from Am J Obstet Gynecol 2021;224(4):368.e1–368.e8)

In the United States, more than 50% of cervical cancers occur in inadequately screened patients. Social and structural determinants of health contribute to inadequate screening rates.
Now Is Our Time to Act: Why Academic Medicine Must Embrace Community Collaboration as Its Fourth Mission
Authors: Alberti Philip , Fair Malika , Skorton David J.
Published: August 2021

In his Leadership Plenary at the Association of American Medical Colleges (AAMC) annual meeting, “Learn Serve Lead 2020: The Virtual Experience,” president and CEO David Skorton emphasized that the traditional tripartite mission of academic medicine—medical education, clinical care, and research—is no longer enough to achieve health justice for all. Today, collaborating with diverse communities deserves equal weight among academic medicine’s missions. This means going beyond “delivering care” to establishing and expanding ongoing, two-way community dialogues that push the envelope of what is possible in service to what is needed. It means appreciating community assets and creating ongoing pathways for listening to and learning from the needs, lived experiences, perspectives, and wisdom of patients, families, and communities. It means working with community-based organizations in true partnership to identify and address needs, and jointly develop, test, and implement solutions. This requires bringing medical care and public/population health concepts together and addressing upstream fundamental causes of health inequities.

The authors call on academic medical institutions to do more to build a strong network of collaborators across public and population health, government, community groups, and the private sector. We in academic medicine must hold ourselves accountable for weaving community collaborations consistently throughout research, medical education, and clinical care. The authors recognize the AAMC can do better to support its member institutions in doing so and discuss new initiatives that signify a shift in emphasis through the association’s new strategic plan and AAMC Center for Health Justice. The authors believe every area of academic medicine could grow and better serve communities by listening and engaging more and bringing medical care, public health, and other sectors closer together.
Climate Change and Medical Education: An Integrative Model
Authors: Sullivan James K. , Lowe Katherine E. , Gordon Ilyssa O. , Colbert Colleen Y. , Salas Renee N. , Bernstein Aaron , Utech Jon , Natowicz Marvin R. , Mehta Neil , Isaacson J. Harry
Published: August 2021

Medical schools face a challenge when trying to include new topics, such as climate change and health (CCH), in their curricula because of competing demands from more traditional biomedical content. At the same time, an understanding of CCH topics is crucial for physicians as they have clear implications for clinical practice and health care delivery. Although some medical schools have begun to incorporate CCH into curricula, the inclusion usually lacks a comprehensive framework for content and implementation. The authors propose a model for integrating CCH into medical school curricula using a practical, multistakeholder approach designed to mitigate competition for time with existing content by weaving meaningful CCH examples into current curricular activities. After the authors identified stakeholders to include in their curricular development working group, this working group determined the goals and desired outcomes of the curriculum; aligned those outcomes with the school’s framework of educational objectives, competencies, and milestones; and strove to integrate CCH goals into as many existing curricular settings as possible. This article includes an illustration of the proposed model for one of the curricular goals (understanding the impacts of climate change on communities), with examples from the CCH curriculum integration that began in the fall of 2020 at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University. The authors have found that this approach does minimize competition for time with existing content and allows mapping of content to existing curricular competencies and milestones, while encouraging a broad understanding of CCH in the context of individual patients, populations, and communities. This model for curricular integration can be applied to other topics such as social determinants of health, health equity, disability studies, and structural racism.
Associations Between Neck and Shoulder Pain and Neuropathic Pain in a Middle-aged Community-living Population
Authors: Machino Masaaki , Ando Kei , Kobayashi Kazuyoshi , Nakashima Hiroaki , Ito Sadayuki , Morozumi Masayoshi , Kanbara Shunsuke , Segi Naoki , Tomita Hiroyuki , Koshimizu Hiroyuki , Seki Taisuke , Ishizuka Shinya , Takegami Yasuhiko , Hasegawa Yukiharu , Imagama Shiro
Published: August 2021

Study Design.

A cross-sectional study.

Objective.

The present study aimed to investigate the prevalence of NeP in subjects suffering from NSP to reveal the impact of NeP on the health-related QOL (HRQOL) in middle-aged and elderly people with NSP in a health checkup.

Summary of Background Data.

No previous studies have established the relationship between NSP and NeP as potential risk factors contributing to a decreased QOL in the general population.

Methods.

The present study involved 203 participants (men: 84, women: 119; mean age: 63.3 yr). For each subject, anthro-pometric measurements, physical function examinations, and blood testing were performed. A cut-off score of >0 on the short-form spine painDETECT questionnaire defined the presence of NeP. Subsequently, the NSP (+) subjects were divided into 2 sub-groups: the NeP (+) and NeP (−) groups. For the assessment of QOL, the short form 36 health survey and the EuroQol 5 dimension 5 level version (EQ-5D-5L) tool were used.

Results.

The study included 100 NSP (+) and 103 NSP (−) subjects. Among the NSP (+) subjects, 46 and 54 subjects were found to be NeP (+) and NeP (−), respectively. For the short form 36 health survey, the multivariate regression analysis revealed that the prevalence of NeP was associated with a lower physical QOL (OR 3.56) and lower mental QOL (OR 4.04). Similarly, the NeP prevalence was found to be the predictor for low QOL scores in EQ-5D-5L (EQ-5D-5L index value <0.875; OR 3.61).

Conclusion.

The prevalence of NeP was reported to be 46.0% in healthy middle-aged and elderly population suffering from NSP, where it was associated with poor HRQOL. Therefore, strategies aimed at alleviating NeP may contribute significantly to the improvement of QOL in middle-aged and elderly people with NSP.

Level of Evidence: 2
Risk of Dementia and Structural Brain Changes Following Nonneurological Infections During 9-Year Follow-Up*
Authors: Peters van Ton Annemieke M. , Meijer-van Leijsen Esther M. C. , Bergkamp Mayra I. , Bronkhorst Ewald M. , Pickkers Peter , de Leeuw Frank-Erik , Tuladhar Anil M. , Abdo Wilson F.
Published: August 2021

OBJECTIVES:

Given the strong association between systemic inflammation and cognitive decline, we aimed to determine whether nonneurologic infections are associated with accelerated cognitive decline and structural changes in the brain using pre- and post-infection neuropsychologic assessments and repeated brain MR images.

DESIGN:

Additional analysis of the prospective observational Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort study.

SETTING:

Single-center study at the Radboud university medical center, Nijmegen, The Netherlands, between January 2006 and September 2015.

PATIENTS:

Five-hundred three participants (50–85 yr old) with cerebral small vessel disease were included and followed for 9 years.

MEASUREMENTS AND MAIN RESULTS:

Participants underwent repeated cognitive measurements and brain MRI. Infectious events were collected. Sepsis episodes were analyzed, and additionally, patients were stratified in three groups: having had a severe infectious episode (e.g., sepsis or hospitalization for infection), a mild, or no infectious episode. Development of dementia, trajectories of cognition, and structural brain changes on MRI in the subsequent follow-up periods were compared between the groups. Complete infectious data were available from 331 patients (mean age 64 ± 8 yr, 57% males). Twenty-nine participants (9%) suffered from a sepsis episode, 69 (21%) from a severe, 201 (61%) from a mild, and 61 (18%) had no infectious episode during follow-up. After correction for age, baseline cognition, and brain volume, each sepsis episode remained associated with an 82% increased risk to develop dementia within the follow-up period (hazard ratio, 1.82; 95% CI, 1.07–3.10; p = 0.027). Infections had no effect on the trajectory of structural changes to the brain after correction for baseline differences.

CONCLUSIONS:

In this 9-year observational follow-up study, sepsis episodes were associated with subsequent development of dementia. Nonneurologic infections had no effect on the trajectory of structural cerebral changes.
COVID-19 vaccination mimicking lymph-node progression in a patient with melanoma: a case report
Authors: Indini Alice , Costa Stefano , Ierardi Anna Maria , Rijavec Erika , Passoni Emanuela , Grossi Francesco
Published: August 2021

COVID-19 vaccination has been rapidly implemented among patients with cancer. We present the case of a patient with high-risk resected cutaneous melanoma, who was a candidate for adjuvant treatment, with postsurgery 18-fluorodeoxyglucose (FDG) PET/computed tomography (CT) scan showing positive axillary lymph nodes after COVID-19 vaccination. This report presents a 50-year-old man with a history of stage IIA cutaneous melanoma. During follow-up, the patient experienced subcutaneous and lymph-node disease progression, documented with 18FDG PET/CT scan. The patient underwent laparoscopic left para-aortic lymphadenectomy and excision of subcutaneous lesion. Histologic examination showed presence of melanoma metastases in 2 lymph nodes out of total 17 excised and neoplastic emboli to the subcutaneous tissue. In view of starting adjuvant nivolumab, the patient underwent CT scan restaging, with evidence of suspect centimetric periaortic and paracaval lymph nodes, which were deemed worthy of 18FDG PET investigation. The 18FDG PET/CT was negative for abdominal hypercaptation, but showed left axillary pathologic lymph nodes. The medical history of the patient revealed that he had received intramuscular Moderna COVID-19 mRNA vaccine in the left deltoid, one week before 18FDG PET examination. Since the patient’s clinical examination was negative and suspecting postvaccination false-positive adenopathy, bilateral axillary ultrasound was performed, excluding the presence of pathologic lymph nodes. The patient has started adjuvant treatment with nivolumab, which is currently ongoing. This case demonstrates unexpected findings in response to COVID-19 vaccination in a patient with melanoma. In this specific case, the detection of 18FDG PET hypercaptation could significantly change the patient’s management. With growing evidence about the pattern and occurrence of adenopathies after mRNA COVID-19 vaccination, recommendations for scheduling and interpretation of 18FDG PET/CT scans among cancer patients will be implemented, in order to reduce equivocal findings and improve outcomes.
Diagnostic Accuracy of Anti-CN1A on the Diagnosis of Inclusion Body Myositis. A Hierarchical Bivariate and Bayesian Meta-analysis
Authors: Mavroudis Ioannis , Knights Mark , Petridis Foivos , Chatzikonstantinou Symela , Karantali Eleni , Kazis Dimitrios
Published: August 2021

Sporadic inclusion body myositis (IBM) is an acquired muscle disease and the most common idiopathic inflammatory myopathy over the age of 50. It is characterized by male predominance, with a prevalence rate between 1 and 71 cases per million, reaching 139 cases per million over the age of 50 globally. The diagnosis of IBM is based on clinical presentation and muscle biopsy findings. However, there is increasing evidence for the role of genetics and serum biomarkers in supporting a diagnosis. Antibodies against the cytosolic 5′-nucleotidase 1A (Anti-CN1A), an enzyme catalyzing the conversion of adenosine monophosphate into adenosine and phosphate and is abundant in skeletal muscle, has been reported to be present in IBM and could be of crucial significance in the diagnosis of the disease. In this study, we investigated the diagnostic accuracy of anti-CN1A antibodies for sporadic IBM in comparison with other inflammatory myopathies, autoimmune disorders, motor neurone disease, using a hierarchical bivariate approach, and a Bayesian model taking into account the variable prevalence. The results of the present analysis show that anti-CN1A antibodies have moderate sensitivity, and despite having high specificity, they are not useful biomarkers for the diagnosis of IBM, polymyositis or dermatomyositis, other autoimmune conditions, or neuromuscular disorders. Neither the hierarchical bivariate nor the Bayesian analysis showed any significant usefulness of anti-CN1A antibodies in the diagnosis of IBM.
Mononeuropathy Multiplex After COVID-19
Authors: Carberry Nathan , Badu Helen , Ulane Christina M. , Beckley Akinpelumi , Rosenberg Samuel J. , Brenner Keith , Brannagan Thomas H.
Published: August 2021

Objectives:

COVID-19 is a novel coronavirus that emerged in 2019 and is responsible for a global pandemic. Numerous neurologic manifestations have been described in the literature regarding COVID-19, but most studies are focused on the central nervous system. The authors have noted an association between prior COVID-19 infection and the development of a systemic neuropathy that manifests with asymmetric sensorimotor loss in the peripheral nervous system. We describe 4 cases of mononeuropathy multiplex that were diagnosed after COVID-19 infection.

Methods:

All patients included were treated for severe COVID-19 infection at New York Presbyterian Hospital and subsequently referred to the Columbia Peripheral Neuropathy Center for persistent neuropathy.

Results:

Patient history, COVID-19 disease course, and mononeuropathy multiplex diagnostic evaluation of the 4 patients are recounted.

Conclusions:

We postulate a connection between COVID-19 and the development of mononeuropathy multiplex with implications in prognostication, rehabilitation strategies, and future treatments.
Punctate Pattern and Pemphigus: Is There Any Evidence of Punctate Pattern Among Iranian Patients?
Authors: Esmaili Nafiseh , Kamyab Kambiz , Hatami Parvaneh , Behrouzifar Shirin , Daneshpazhooh Maryam , Tavakolpour Soheil , Goodarzi Azadeh , Mortazavi Hossein , Aryanian Zeinab
Published: August 2021

Pemphigus is an autoimmune blistering disease. Direct immunofluorescence (DIF) of the perilesional skin is one of the most effective techniques and probably the gold standard in the diagnosis of pemphigus. A specific punctate immunofluorescence pattern has been recently reported.

Aim:

To examine the prevalence of this novel pattern among Iranian patients with pemphigus and peruse the relationship between the presence of a punctate pattern with clinical severity of disease and histopathological findings.

Methods:

One hundred recently diagnosed patients with pemphigus were enrolled. DIF evaluation and routine light microscopy were performed on their biopsy specimens. Disease severity was determined using the Pemphigus Disease Area Index. Serum samples were collected to measure autoantibody titers using enzyme-linked immunosorbent assay.

Results:

All the samples evaluated by DIF showed a continuous linear pattern of intercellular IgG deposition, whereas none of them had a punctate pattern. Despite a significant correlation between the Pemphigus Disease Area Index score and autoantibody values, no association between histopathological findings and disease severity has been found.

Conclusion:

We could not detect any punctate pattern among Iranian patients with pemphigus. The importance of this pattern in the diagnosis of pemphigus might be different among patients with different ethnic and genetic factors.
Early Erythema Migrans: Do Not Count on Plasma Cells
Authors: Brem Candice E. , Goldberg Lynne J.
Published: August 2021

Three hundred thousand new cases of Lyme disease are diagnosed annually in the United States. The earliest manifestation of the disease, erythema migrans, occurs earlier than serologic conversion, and skin biopsies can be very helpful in suggesting the diagnosis. Histopathologic findings vary depending on where in the lesion the specimen is taken, but typically consist of a superficial and deep perivascular and interstitial lymphocytic infiltrate with eosinophils centrally and with histiocytes and plasma cells at the periphery. Rare cases with interstitial histiocytes and rare-to-sparse plasma cells exist. We present a 67-year-old man whose skin biopsy, taken on day 2 of his eruption, demonstrated a subtle perivascular and interstitial infiltrate of histiocytes without plasma cells. Dermatopathologists need to be aware of this pattern and consider the diagnosis of erythema migrans, despite negative initial serologic testing.
Use of Absorbable Dermal Stapler in Reduction Mammoplasty: Assessing Technical, Quality-of-Life, and Aesthetics Outcomes
Authors: Patel Viren , Green Jason L. , Christopher Adrienne N. , Morris Martin P. , Weiss Eric S. , Broach Robyn B. , Butler Paris D.
Published: August 2021

Introduction:

Reduction mammaplasty is a mainstay in the treatment of symptomatic macromastia, with a well-described positive impact on patient quality-of-life (QoL). Absorbable dermal staplers have the potential to improve the efficiency of skin closure in reduction mammoplasties, but a more comprehensive assessment of its impact on key outcomes has not been fully elucidated.

Methods:

A retrospective review of patients undergoing reduction mammoplasty between November 2018 and December 2020 was conducted. Patients were included if they had undergone a wise-pattern reduction with a superomedial pedicle and completed 3 months of follow-up. Patient demographics, operative information, clinical and aesthetic outcomes, and QoL were compared between patients that had INSORB stapler-assisted and suture-only closures.

Results:

Seventy-five patients met the inclusion criteria, with 34 patients (45%) in the stapler cohort. Total procedure time was significantly reduced with the use of the dermal stapler (stapler: 154 vs. suture: 170 minutes; p = 0.003). The incidence of major complications was similar between cohorts (stapler: 8.8% vs. suture: 12%; p = 0.64), as was the incidence of minor complications (stapler: 44% vs. suture: 41%; p = 0.82). Regardless of closure technique, patients demonstrated significant increases in all QoL domains (p <0.001). Lastly, 10 independent raters found no difference in the cosmetic appearance of breasts from either cohort, when judging overall breast appearance, shape, scars, volume and the nipple-areolar complex (all p > 0.05).

Conclusions:

The dermal stapler improves efficiency of closure during reduction mammoplasty without increasing the incidence of wound healing complications. Additionally, cosmetic outcomes are not affected, and patients demonstrate similar post-operative satisfaction with the result regardless of closure technique.