bluuebunny/crossref_metadata_2025 huggingface dataset:
Mass-Cytometry-Based Quantification of Global Histone Post-Translational Modifications at Single-Cell Resolution Across Peripheral Immune Cells in IBD
Authors: Bai Lawrence , Dermadi Denis , Kalesinskas Laurynas , Dvorak Mai , Chang Sarah E , Ganesan Ananthakrishnan , Rubin Samuel J S , Kuo Alex , Cheung Peggie , Donato Michele , Utz Paul J , Habtezion Aida , Khatri Purvesh
Published: December 2022

Background and Aims

Current understanding of histone post-translational modifications [histone modifications] across immune cell types in patients with inflammatory bowel disease [IBD] during remission and flare is limited. The present study aimed to quantify histone modifications at a single-cell resolution in IBD patients during remission and flare and how they differ compared to healthy controls.

Methods

We performed a case-control study of 94 subjects [83 IBD patients and 11 healthy controls]. IBD patients had either ulcerative colitis [n = 38] or Crohn’s disease [n = 45] in clinical remission or flare. We used epigenetic profiling by time-of-flight [EpiTOF] to investigate changes in histone modifications within peripheral blood mononuclear cells from IBD patients.

Results

We discovered substantial heterogeneity in histone modifications across multiple immune cell types in IBD patients. They had a higher proportion of less differentiated CD34+ haematopoietic progenitors, and a subset of CD56bright natural killer [NK] cells and γδ T cells characterized by distinct histone modifications associated with gene transcription. The subset of CD56bright NK cells had increases in several histone acetylations. An epigenetically defined subset of NK cells was associated with higher levels of C-reactive protein in peripheral blood. CD34+ monocytes from IBD patients had significantly decreased cleaved H3T22, suggesting they were epigenetically primed for macrophage differentiation.

Conclusion

We describe the first systems-level quantification of histone modifications across immune cells from IBD patients at a single-cell resolution, revealing the increased epigenetic heterogeneity that is not possible with traditional ChIP-seq profiling. Our data open new directions in investigating the association between histone modifications and IBD pathology using other epigenomic tools.
Smartphone-activated volunteer responders and bystander defibrillation for out-of-hospital cardiac arrest in private homes and public locations
Authors: Andelius Linn , Malta Hansen Carolina , Jonsson Martin , Gerds Thomas A , Rajan Shahzleen , Torp-Pedersen Christian , Claesson Andreas , Lippert Freddy , Tofte Gregers Mads Chr , Berglund Ellinor , Gislason Gunnar H , Køber Lars , Hollenberg Jacob , Ringh Mattias , Folke Fredrik
Published: December 2022

Aims

To investigate the association between the arrival of smartphone-activated volunteer responders before the Emergency Medical Services (EMS) and bystander defibrillation in out-of-hospital cardiac arrest (OHCA) at home and public locations.

Methods and results

This is a retrospective study (1 September 2017–14 May 2019) from the Stockholm Region of Sweden and the Capital Region of Denmark. We included 1271 OHCAs, of which 1029 (81.0%) occurred in private homes and 242 (19.0%) in public locations. The main outcome was bystander defibrillation. At least one volunteer responder arrived before EMS in 381 (37.0%) of OHCAs at home and 84 (34.7%) in public. More patients received bystander defibrillation when a volunteer responder arrived before EMS at home (15.5 vs. 2.2%, P < 0.001) and in public locations (32.1 vs. 19.6%, P = 0.030). Similar results were found among the 361 patients with an initial shockable heart rhythm (52.7 vs. 11.5%, P < 0.001 at home and 60.0 vs. 37.8%, P = 0.025 in public). The standardized probability of receiving bystander defibrillation increased with longer EMS response times in private homes. The 30-day survival was not significantly higher when volunteer responders arrived before EMS (9.2 vs. 7.7% in private homes, P = 0.41; and 40.5 vs. 35.4% in public locations, P = 0.44).

Conclusion

Bystander defibrillation was significantly more common in private homes and public locations when a volunteer responder arrived before the EMS. The standardized probability of bystander defibrillation increased with longer EMS response times in private homes. Our findings support the activation of volunteer responders and suggest that volunteer responders could increase bystander defibrillation, particularly in private homes.
Tumour location predicts occult N1 nodal metastasis in clinical stage I non-small-cell lung cancer
Authors: Kawamoto Nobutaka , Tsutani Yasuhiro , Kamigaichi Atsushi , Ohsawa Manato , Mimae Takahiro , Miyata Yoshihiro , Okada Morihito
Published: December 2022

OBJECTIVES

Pathological lymph node metastases are often observed in patients with clinical N0 lung cancer. Identifying preoperative predictors of occult hilar nodal metastasis (OHNM) is important in determining the surgical procedure in patients with clinical stage I non-small-cell lung cancer. This study aimed to determine the frequency and predictors of OHNM by tumour location in these patients.

METHODS

Between April 2007 and May 2019, data of patients who underwent lobectomy or segmentectomy for clinical stage I pure-solid non-small-cell lung cancer were retrospectively reviewed. The ratio of the distance from the pulmonary hilum to the proximal side of the tumour to the distance from the pulmonary hilum to the visceral pleural surface through the centre of the tumour, named ‘distance ratio (DR)’, was calculated. The relationship of the DR with clinicopathological findings and prognosis was discussed.

RESULTS

A total of 357 patients were enrolled. OHNM frequency was 14.6%. Patients were divided into 2 groups based on whether the DR was ≤0.67 (central type) or >0.67 (peripheral type). The frequency of OHNM was significantly higher in the DR ≤0.67 group (21.5% vs 7.4%; P < 0.001). Multivariable analysis revealed that DR was the only independent preoperative predictor of OHNM (odds ratio, 3.63; 95% confidence interval, 1.83–7.18; P < 0.001).

CONCLUSIONS

The frequency of OHNM was significantly lower in peripheral-type lung cancer; therefore, tumour location was the most important preoperative predictor of OHNM.
B-Cell Responses in Chronic Chagas Disease: Waning of Trypanosoma cruzi–Specific Antibody-Secreting Cells Following Successful Etiological Treatment
Authors: Cesar G , Natale M A , Albareda M C , Alvarez M G , Lococo B , De Rissio A M , Fernandez M , Castro Eiro M D , Bertocchi G , White B E , Zabaleta F , Viotti R , Tarleton R L , Laucella S A
Published: December 2022

Background

A drawback in the treatment of chronic Chagas disease (American trypanosomiasis) is the long time required to achieve complete loss of serological reactivity, the standard for determining treatment efficacy.

Methods

Antibody-secreting cells and memory B cells specific for Trypanosoma cruzi and their degree of differentiation were evaluated in adult and pediatric study participants with chronic Chagas disease before and after etiological treatment.

Results

T. cruzi–specific antibody-secreting cells disappeared from the circulation in benznidazole or nifurtimox-treated participants with declining parasite-specific antibody levels after treatment, whereas B cells in most participants with unaltered antibody levels were low before treatment and did not change after treatment. The timing of the decay in parasite-specific antibody-secreting B cells was similar to that in parasite-specific antibodies, as measured by a Luminex-based assay, but preceded the decay in antibody levels detected by conventional serology. The phenotype of total B cells returned to a noninfection profile after successful treatment.

Conclusions

T. cruzi–specific antibodies in the circulation of chronically T. cruzi–infected study participants likely derive from both antigen-driven plasmablasts, which disappear after successful treatment, and long-lived plasma cells, which persist and account for the low frequency and long course to complete seronegative conversion in successfully treated participants.
Emerging Therapies for Full-Thickness Skin Regeneration
Authors: Palmieri Tina L
Published: December 2022

The classical treatment of extensive full-thickness skin loss due to trauma or burns has been the split-thickness skin graft. While split-thickness skin grafts close the wound, they leave patients with visible scars, dry skin, pruritis, pain, pigmentation alterations, and changes in sensation. The optimal replacement for full-thickness skin loss is replacement with intact full-thickness skin. New technologies combined with advances in the understanding of the mechanisms behind wound healing have led to the development of techniques and products that may eventually recapitulate the functions, appearance, and physical properties of normal skin. Autologous homologous skin constructs, minimal functional skin units, and composite bioengineered skin with dermal substitutes all represent potential avenues for full-thickness composite skin development and application in extensive wounds. This article summarizes the progress, state, and future of full-thickness skin regeneration in burn and massive wound patients.
Advances in Skin Tissue Engineering and Regenerative Medicine
Authors: Jorgensen Adam M , Mahajan Naresh , Atala Anthony , Murphy Sean V
Published: December 2022

There are an estimated 500,000 patients treated with full-thickness wounds in the United States every year. Fire-related burn injuries are among the most common and devastating types of wounds that require advanced clinical treatment. Autologous split-thickness skin grafting is the clinical gold standard for the treatment of large burn wounds. However, skin grafting has several limitations, particularly in large burn wounds, where there may be a limited area of non-wounded skin to use for grafting. Non-cellular dermal substitutes have been developed but have their own challenges; they are expensive to produce, may require immunosuppression depending on design and allogenic cell inclusion. There is a need for more advanced treatments for devastating burns and wounds. This manuscript provides a brief overview of some recent advances in wound care, including the use of advanced biomaterials, cell-based therapies for wound healing, biological skin substitutes, biological scaffolds, spray on skin and skin bioprinting. Finally, we provide insight into the future of wound care and technological areas that need to be addressed to support the development and incorporation of these technologies.
A Risk-Benefit Review of Currently Used Dermal Substitutes for Burn Wounds
Authors: Hill David M , Hickerson William L , Carter Jeffrey E
Published: December 2022

While split-thickness autologous skin grafts remain the most common method of definitive burn wound closure, dermal substitutes have emerged as an attractive option. There are many advantages of utilizing a dermal substitute, notably reducing the need for donor tissue and subsequent iatrogenic creation of a secondary wound. However, there are disadvantages with each that most be weighed and factored into the decision. And most come at a high initial financial cost. There is little comparative literature of the various available and emerging products. This analysis was performed to objectively present risks and benefits of each option.
Use of Dermal Regenerative Templates for Burns
Authors: Mason Stephanie A , Pham Tam N
Published: December 2022

Autologous skin grafting has permitted survival and restoration of function in burn injuries of ever larger total body surface area (TBSA) sizes. However, the goal of replacing “like with like” skin structures is often impossible because full-thickness donor harvesting requires primary closure at the donor site for it to heal. Split-thickness skin grafting (STSG), on the other hand, only harvests part of the dermis at the donor site, allowing it to re-epithelialize on its own. The development of the first dermal regenerative template (DRT) in the late 1970s represented a major advance in tissue engineering that addresses the issue of insufficient dermal replacement when STSGs are applied to the full-thickness defect. This review aims to provide an overview of currently available DRTs in burn management from a clinician’s perspective. It focuses on the main strengths and pitfalls of each product and provides clinical pearls based on clinical experience and evidence.
Surgical Repair of the Acute Burn Wound: Who, When, What Techniques? What Is the Future?
Authors: Leon-Villapalos Jorge , Barret Juan P
Published: December 2022

Modern burns surgery is multidisciplinary, multimodal and includes a dermal preservation approach. The management of the surgical wound starts in the pre-hospital environment with stabilization and assessment of the burn injured patient according to protocols of trauma resuscitation with special emphasis in the assessment of the burn depth and surface area. A large burn requires fluid resuscitation and physiological support, including counterbalancing hyper metabolism, fighting infection and starting a long burns intensive care journey. A deep burn may impose the need for surgical debridement and cover through a staged approach of excision of devitalized tissue depending on its extension and patient circumstances. These methodologies warrant patients survivability and require professionals integrated in a multidisciplinary team sharing decisions and directing management. Burns Multimodality involves multiple techniques used according to patient’s needs, wound environment, operators experience and available resources. Traditional practices used together with new techniques may reduce morbidity and operative time but also challenge stablished practice. The concept of using the best teams with the best techniques combines with the need for selective and judicious surgery that preserves tissue architecture and spares as much as possible dermal component, therefore reducing the possibility of functional impairment and cosmetic embarrassment caused by pathological scars. Who is best placed to perform these tasks, the appropriate or best timing of surgery and the different practices used to achieve best results will be discussed, together with a reflection on what the future holds for these fundamental steps in the management of the burn injured patient turning into a functional burn survivor.
Mentoring in the USDA Forest Service: A Survey of Aquatic Professionals
Authors: Cerveny Lee , Baral Nabin , Penaluna Brooke , Roper Brett , Shively Daniel , Witt Shelly
Published: December 2022

Mentoring is suggested as an important strategy to promote workplace inclusivity and is shown to be positively associated with high employee morale, yet mentee needs and experiences may not be universal. To evaluate mentoring impacts from the perspective of USDA Forest Service employees, we conducted an online survey of 251 aquatic professionals, including managers and scientists. 70% of respondents had mentors, and mentorship status did not vary across demographic characteristics. Previous mentoring relationships were most frequently identified as “informal” rather than “formal”; female employees were more likely to desire formal mentoring. Mentored respondents found their work more challenging, fulfilling, and valuable than unmentored respondents. Mentees looked for mentors who could provide constructive feedback, speak candidly, use active listening skills, and who cared about their careers. Overall, respondents were satisfied with their mentors’ skills. Despite strong demand for mentoring, access to mentors among aquatic professionals appears low across all categories.
Desmoid fibromatosis infiltrating left adrenal gland and kidney
Authors: Tee Sui Wu , Richards Avisha , Tan Yi Han , Jeyabalan Dhinisya , Durairaj Gunaseelan
Published: December 2022

Desmoid fibromatosis is a rare, benign, locally aggressive fibroblastic proliferation that may occur in almost any anatomical location. Due to its rarity and unpredictable clinical course, there has not been a standard guideline of treatment. We encountered a case of desmoid fibromatosis in our centre. A young lady previously fit and well was referred for a symptomatic, rapidly growing left sided abdominal mass. Otherwise, she denied any bowel related symptoms or constitutional manifestation. Imaging demonstrated a large well-defined lobulated solid-cystic mass extending from vertebral level T10 to L5, measuring 10.5 cm × 15 cm × 23 cm. The mass was in close proximity with the left adrenal gland, left kidney, pancreas and spleen. Ultrasound guided biopsy interpreted it as a fibroblastic or myelofibroblastic tumour, favouring desmoid fibromatosis. Surgery was then performed where the mass was removed along with the left adrenal gland and kidney. Post-operative care was complicated with pulmonary embolism, hospital-acquired pneumonia and pancreatitis.
The ASAS-SN catalogue of variable stars X: discovery of 116 000 new variable stars using G-band photometry
Authors: Christy C T , Jayasinghe T , Stanek K Z , Kochanek C S , Thompson T A , Shappee B J , Holoien T W-S , Prieto J L , Dong Subo , Giles W
Published: December 2022

The All-Sky Automated Survey for Supernovae (ASAS-SN) is the first optical survey to monitor the entire sky, currently with a cadence of ≲ 24 h down to g ≲ 18.5 mag. ASAS-SN has routinely operated since 2013, collecting ∼ 2 000 to over 7 500 epochs of V- and g-band observations per field to date. This work illustrates the first analysis of ASAS-SN’s newer, deeper, and higher cadence g-band data. From an input source list of ∼55 million isolated sources with g < 18 mag, we identified 1.5 × 106 variable star candidates using a random forest (RF) classifier trained on features derived from Gaia, 2MASS, and AllWISE. Using ASAS-SN g-band light curves, and an updated RF classifier augmented with data from Citizen ASAS-SN, we classified the candidate variables into eight broad variability types. We present a catalogue of ∼116 000 new variable stars with high-classification probabilities, including ∼111 000 periodic variables and ∼5 000 irregular variables. We also recovered ∼263 000 known variable stars.
Perceptions and Reality of Antimicrobial Prescribing During the Transition to Comfort Measures Only at an Academic Medical Center
Authors: Larnard Jeffrey , Blackshear Leslie , Lee Matthew Shou Lun , Buss Mary K , Stead Wendy
Published: December 2022

Background

Little is known about antimicrobial prescribing when patient care is transitioned to comfort measures only (CMO). We used a multidisciplinary survey and retrospective cohort study to gain insight into antimicrobial prescribing in this population at an academic medical center to inform future antimicrobial stewardship interventions.

Methods

A survey focusing on antimicrobial prescribing during the transition to CMO was electronically distributed to providers in medical subspecialities and responses were compared across specialties. A retrospective chart review was performed of patients admitted to an academic medical center in 2020 who were on antimicrobials in the 48 hours prior to CMO. We investigated the percentage of patients who remained on antimicrobials after the transition to CMO and rationale for continuing antimicrobials.

Results

We received 113 survey responses (35% response rate). Forty-one percent of respondents indicated that they “sometimes” or “often” continued antimicrobials during the transition to CMO. Patient/family preference and symptom palliation were the most common factors cited by respondents when deciding whether to continue antimicrobials in this population. Of the 546 patient charts reviewed, 140 (26%) patients were alive 48 hours after CMO order, and 19 (14%) of those patients remained on antimicrobials. Five of 19 (26%) patients had documentation that antimicrobials were continued due to patient/family preference and 5 of 19 (26%) patients had documentation that antimicrobials were continued for palliation of symptoms.

Conclusions

Patient/family preference and symptom palliation are important factors in prescribing antimicrobials when patient care is transitioned to CMO. More evidence is needed regarding palliative benefits of antibiotics to inform provider discussions of benefits and harms of antimicrobial use in this setting.
Do Unjust States Have the Standing to Blame? Three Reservations About Scepticism
Authors: Ewing Benjamin
Published: December 2022

If an offender was treated unjustly by her state in a way that curtailed her options or otherwise made it more likely she would commit her crime, does her state have the moral standing to blame her for that crime? Many theorists have expressed scepticism that the state does. I present three reservations about such scepticism. First, much of it appears to derive its intuitive appeal from problems with the content of state condemnation that can be solved by changing its content rather than its source. Second, adequate legal recognition of everyone’s fundamental moral rights arguably requires not merely the proscription of violations of those rights, but authoritative public condemnation of such violations, which only the state is capable of supplying. Finally, an unjust state would not do disadvantaged offenders any favours by holding its tongue—nor would such offenders help themselves by closing their ears to its criticism.
Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGF-β and PD-L1, in Patients with Non-Small Cell Lung Cancer Resistant or Refractory to Immune Checkpoint Inhibitors
Authors: Barlesi Fabrice , Isambert Nicolas , Felip Enriqueta , Cho Byoung Chul , Lee Dae Ho , Peguero Julio , Jerusalem Guy , Penel Nicolas , Saada-Bouzid Esma , Garrido Pilar , Helwig Christoph , Locke George , Ojalvo Laureen S , Gulley James L
Published: December 2022

Background

Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of transforming growth factor beta receptor II (a TGF-β “trap”) fused to a human immunoglobulin G1 monoclonal antibody blocking programmed cell death 1 ligand 1 (PD-L1). We report the efficacy and safety in patients with non-small cell lung cancer (NSCLC) that progressed following anti-PD-(L)1 therapy.

Materials and Methods

In this expansion cohort of NCT02517398—a global, open-label, phase I trial—adults with advanced NSCLC that progressed following chemotherapy and was primary refractory or had acquired resistance to anti-PD-(L)1 treatment received intravenous bintrafusp alfa 1200 mg every 2 weeks until confirmed progression, unacceptable toxicity, or trial withdrawal. The primary endpoint was best overall response (by Response Evaluation Criteria in Solid Tumors version 1.1 adjudicated by independent review committee); secondary endpoints included safety.

Results

Eighty-three eligible patients (62 [74.7%] treated with ≥3 prior therapies) received bintrafusp alfa. Four patients (3 primary refractory, 1 acquired resistant) had confirmed partial responses (objective response rate, 4.8%; 95% CI, 1.3%-11.9%), and 9 had stable disease. Tumor cell PD-L1 expression was not associated with response. Nineteen patients (22.9%) experienced grade ≥3 treatment-related adverse events, most commonly asthenia (3 [3.6%]) and fatigue, eczema, and pruritus (2 each [2.4%]). One patient had grade 4 amylase increased. One patient died during treatment for pneumonia before initiation of bintrafusp alfa.

Conclusion

Although the primary endpoint was not met, bintrafusp alfa showed some clinical activity and a manageable safety profile in patients with heavily pretreated NSCLC, including prior anti-PD-(L)1 therapy. Tumor responses occurred irrespective of whether disease was primary refractory or had acquired resistance to prior anti-PD-(L)1 therapy.
Weak genetic structure, shared nonbreeding areas, and extensive movement in a declining waterbird
Authors: Shephard Nicholas G , Szczys Patricia , Moore David J , Reudink Matthew W , Costa Jeffrey N , Bracey Annie M , Lisovski Simeon , McKellar Ann E
Published: December 2022

Understanding population mixing, movements, and connectivity of populations is an important first step towards effective conservation, particularly for long distance migrants that are suffering the greatest population declines, as this allows researchers to recognize how populations may face different risks throughout the annual cycle. We combined population genetic and individual tracking data to quantify the genetic structure and full-cycle movements of the declining North American Black Tern (Chlidonias niger surinamensis). A total of 147 genetic samples were collected from 9 breeding colonies across the range (Maine, Ontario, Michigan, Iowa, Wisconsin, Nebraska, Saskatchewan, and Oregon), and 19 light-level geolocators were recovered from 3 colonies (Ontario, Michigan, and Saskatchewan). Our results demonstrated weak genetic structure, and tracking data demonstrated the use of shared nonbreeding areas between central (Saskatchewan) and eastern (Ontario and Michigan) breeding populations. Our tracking data also provide novel evidence of long-distance breeding dispersal (~1,400 km between breeding locations across years) based on an individual tracked across multiple years, as well as short distance dispersal (~2.5–57 km) based on new recovery locations of 6 tracked individuals. Our results are consistent with the hypothesis that the shared use of nonbreeding areas influences physical condition, timing of departure, and subsequent reproductive timing in such a way as to facilitate dispersal across the breeding range and contribute to weak genetic structure among breeding populations. This study is the first to explore population genetics and migration of North American Black Terns. Extensive movement of individuals may pose a challenge from a conservation perspective as important areas and habitats throughout the annual cycle may be difficult to predict, and future studies should build on our work via extensive mark-resight effort using color bands, tracking individuals from more breeding sites, and examining carry-over effects to further investigate when in the annual cycle populations are most limited.
Organic molecule single-photon sources
Authors: Gaither-Ganim Moses B , Newlon Scott A , Anderson Michael G , Lee Bumsu
Published: December 2022

Since the onset of the 1990s, the development of single-molecule spectroscopy has led to the discovery of various quantum optical signatures in organic single molecules. The single-photon nature of an organic chromophore is of particular importance because of its potential as a nonclassical photon source at room temperature for quantum information science and optical quantum computing. This condensed review focuses on the introduction of fundamental knowledge and basic experimental methods for single-photon sources and organic molecular photophysics and summarizes the research developments in this field, providing an understanding of quantum emission from organic single molecules.
Layer-by-layer assembly of procyanidin and collagen promotes mesenchymal stem cell proliferation and osteogenic differentiation in vitro and in vivo
Authors: Bai Zhibiao , Hu Kai , Shou Zeyu , Yu Jiahuan , Meng Hongming , Zhou Han , Chen Liangyan , Yu Tiantian , Lu Ruofei , Li Na , Chen Chun
Published: December 2022

Collagen, commonly used in tissue engineering, is widespread in various tissues. During bone tissue regeneration, collagen can stimulate the cellular response and determine the fate of cells. In this work, we integrated collagen type II with procyanidin (PC) onto an implant coating by applying a layer-by-layer technique to demonstrate that collagen and PC can participate in the construction of new biomaterials and serve as multifunctional components. The effects of PC/collagen multilayers on the viability of cocultured bone marrow mesenchymal stem cells (BMSCs) were analyzed by cell counting kit-8 analysis and phalloidin staining. The reactive oxygen species level of BMSCs was revealed through immunofluorescent staining and flow cytometry. Osteogenesis-related genes were detected, and in vivo experiment was performed to reveal the effect of newly designed material on the osteogenic differentiation of BMSCs. Our data demonstrated that in BMSCs PC/collagen multilayers accelerated the proliferation and osteogenic differentiation through Wnt/β-catenin signaling pathway and enhanced bone generation around the implant in the bone defect model of rabbit femurs. In summary, combination of collagen and PC provided a new sight for the research and development of implant materials or coatings in the future.
Osteochondral regenerative engineering: challenges, state-of-the-art and translational perspectives
Authors: Barui Srimanta , Ghosh Debolina , Laurencin Cato T
Published: December 2022

Despite quantum leaps, the biomimetic regeneration of cartilage and osteochondral regeneration remains a major challenge, owing to the complex and hierarchical nature of compositional, structural and functional properties. In this review, an account of the prevailing challenges in biomimicking the gradients in porous microstructure, cells and extracellular matrix (ECM) orientation is presented. Further, the spatial arrangement of the cues in inducing vascularization in the subchondral bone region while maintaining the avascular nature of the adjacent cartilage layer is highlighted. With rapid advancement in biomaterials science, biofabrication tools and strategies, the state-of-the-art in osteochondral regeneration since the last decade has expansively elaborated. This includes conventional and additive manufacturing of synthetic/natural/ECM-based biomaterials, tissue-specific/mesenchymal/progenitor cells, growth factors and/or signaling biomolecules. Beyond the laboratory-based research and development, the underlying challenges in translational research are also provided in a dedicated section. A new generation of biomaterial-based acellular scaffold systems with uncompromised biocompatibility and osteochondral regenerative capability is necessary to bridge the clinical demand and commercial supply. Encompassing the basic elements of osteochondral research, this review is believed to serve as a standalone guide for early career researchers, in expanding the research horizon to improve the quality of life of osteoarthritic patients affordably.
Emma Pastoral
Authors: Valihora Karen
Published: December 2022

This essay situates the repeating and echoing refrains of Austen’s Emma (1816)—of gruel, draughts, and fires; of ‘poor Miss Taylor’, and ‘poor little Harriet’—within the tradition of classical pastoral. It suggests that the pastoral forms Austen employs at once tend to escape notice and are crucial to understanding what the novel is about. The overhearing of Emma’s thoughts staged in the novel’s free-indirect narration, for example, is approached as a version of the third-person framing of first-person speakers to comic and ironic effect in the earliest pastorals, those of Theocritus, Virgil, and Ovid, as well as in Marvell’s Mower poems. Pastoral’s chief occasion concerns the encounter between poets and shepherds, sophisticated and simple, high and low—and readers and hearers. The many occasions of overhearing through which the novel includes its readers in its world, the friendship between Emma and Harriet, as between Knightley and Robert Martin, the speeches of Miss Bates, the reclusiveness of Mr Woodhouse—all suggest a pastoral poetics. The essay explores how the sense of a golden age of harmony and abundance that marks the daily round of life in Highbury foregrounds reciprocity, equity, and responsiveness, forms of recognition that challenge the rigid stratification and hierarchy of the world of which Austen writes.
Adipose-Derived Stromal Cells for Chronic Wounds: Scientific Evidence and Roadmap Toward Clinical Practice
Authors: Brembilla Nicolo C , Vuagnat Hubert , Boehncke Wolf-Henning , Krause Karl-Heinz , Preynat-Seauve Olivier
Published: December 2022

Chronic wounds, ie, non-healing ulcers, have a prevalence of ~1% in the general population. Chronic wounds strongly affect the quality of life and generate considerable medical costs. A fraction of chronic wounds will heal within months of appropriate treatment; however, a significant fraction of patients will develop therapy-refractory chronic wounds, leading to chronic pain, infection, and amputation. Given the paucity of therapeutic options for refractory wounds, cell therapy and in particular the use of adipose-derived stromal cells (ASC) has emerged as a promising concept. ASC can be used as autologous or allogeneic cells. They can be delivered in suspension or in 3D cultures within scaffolds. ASC can be used without further processing (stromal vascular fraction of the adipose tissue) or can be expanded in vitro. ASC-derived non-cellular components, such as conditioned media or exosomes, have also been investigated. Many in vitro and preclinical studies in animals have demonstrated the ASC efficacy on wounds. ASC efficiency appears to occurs mainly through their regenerative secretome. Hitherto, the majority of clinical trials focused mainly on safety issues. However more recently, a small number of randomized, well-controlled trials provided first convincing evidences for a clinical efficacy of ASC-based chronic wound therapies in humans. This brief review summarizes the current knowledge on the mechanism of action, delivery and efficacy of ASC in chronic wound therapy. It also discusses the scientific and pharmaceutical challenges to be solved before ASC-based wound therapy enters clinical reality.
Mathematical modeling: a study of multidisciplinary benefits in the math classroom
Authors: Luczak Richard , Erwin Rob
Published: December 2022

Math modeling is a unique and powerful part of mathematics that is underutilized in contemporary classrooms. Teachers of all grade levels may utilize such modeling problems to better serve the students in their classrooms, with related analytical problem-solving activities that contribute to learners meeting the highest of learning standards. With a continued focus within mathematics education on critical thinking, creativity, disciplinary literacy and college/career readiness, math modeling is at the forefront of research-tested methods to develop these crucial skills. This is an important direction mathematics education that needs to go in order to prepare students for the future.
Transcriptome mining extends the host range of the Flaviviridae to non-bilaterians
Authors: Mifsud Jonathon C O , Costa Vincenzo A , Petrone Mary E , Marzinelli Ezequiel M , Holmes Edward C , Harvey Erin
Published: December 2022

The flavivirids (family Flaviviridae) are a group of positive-sense RNA viruses that include well-documented agents of human disease. Despite their importance and ubiquity, the timescale of flavivirid evolution is uncertain. An ancient origin, spanning millions of years, is supported by their presence in both vertebrates and invertebrates and by the identification of a flavivirus-derived endogenous viral element in the peach blossom jellyfish genome (Craspedacusta sowerbii, phylum Cnidaria), implying that the flaviviruses arose early in the evolution of the Metazoa. To date, however, no exogenous flavivirid sequences have been identified in these hosts. To help resolve the antiquity of the Flaviviridae, we mined publicly available transcriptome data across the Metazoa. From this, we expanded the diversity within the family through the identification of 32 novel viral sequences and extended the host range of the pestiviruses to include amphibians, reptiles, and ray-finned fish. Through co-phylogenetic analysis we found cross-species transmission to be the predominate macroevolutionary event across the non-vectored flavivirid genera (median, 68 per cent), including a cross-species transmission event between bats and rodents, although long-term virus–host co-divergence was still a regular occurrence (median, 23 per cent). Notably, we discovered flavivirus-like sequences in basal metazoan species, including the first associated with Cnidaria. This sequence formed a basal lineage to the genus Flavivirus and was closer to arthropod and crustacean flaviviruses than those in the tamanavirus group, which includes a variety of invertebrate and vertebrate viruses. Combined, these data attest to an ancient origin of the flaviviruses, likely close to the emergence of the metazoans 750–800 million years ago.
Gender Differences in Informal Labor-Market Resilience
Authors: Hardy Morgan , Litzow Erin , McCasland Jamie , Kagy Gisella
Published: December 2022

This paper reports on the universe of garment-making-firm owners in a Ghanaian district capital during the COVID-19 crisis. By July 2020, 80 percent of both male- and female-owned firms were operational. However, pre-pandemic data show that selection into persistent closure differs by gender. Consistent with a “cleansing effect” of recessions and highlighting the presence of marginal female entrepreneurs, female-owned firms that remain closed past the spring lockdown are negatively selected on pre-pandemic sales. The pre-pandemic sales distributions of female survivors and non-survivors are significantly different from each other. Female owners of non-operational firms exit to non-employment and experience large decreases in overall earnings. In contrast, persistently closed male-owned firms are not selected on pre-pandemic firm characteristics. Instead, male non-survivors are 36 percentage points more likely than male survivors to have another income-generating activity prior to the crisis. Male owners of persistently closed firms fully compensate for revenue losses in their core businesses with earnings from these alternative income-generating activities. Taken together, the evidence is most consistent with differential underlying occupational choice fundamentals for self-employed men and women in this context.
Mechanical Power Ratio and Respiratory Treatment Escalation in COVID-19 Pneumonia: A Secondary Analysis of a Prospectively Enrolled Cohort
Authors: Gattarello Simone , Coppola Silvia , Chiodaroli Elena , Pozzi Tommaso , Camporota Luigi , Saager Leif , Chiumello Davide , Gattinoni Luciano
Published: December 2022

Background

Under the hypothesis that mechanical power ratio could identify the spontaneously breathing patients with a higher risk of respiratory failure, this study assessed lung mechanics in nonintubated patients with COVID-19 pneumonia, aiming to (1) describe their characteristics; (2) compare lung mechanics between patients who received respiratory treatment escalation and those who did not; and (3) identify variables associated with the need for respiratory treatment escalation.

Methods

Secondary analysis of prospectively enrolled cohort involving 111 consecutive spontaneously breathing adults receiving continuous positive airway pressure, enrolled from September 2020 to December 2021. Lung mechanics and other previously reported predictive indices were calculated, as well as a novel variable: the mechanical power ratio (the ratio between the actual and the expected baseline mechanical power). Patients were grouped according to the outcome: (1) no-treatment escalation (patient supported in continuous positive airway pressure until improvement) and (2) treatment escalation (escalation of the respiratory support to noninvasive or invasive mechanical ventilation), and the association between lung mechanics/predictive scores and outcome was assessed.

Results

At day 1, patients undergoing treatment escalation had spontaneous tidal volume similar to those of patients who did not (7.1 ± 1.9 vs. 7.1 ± 1.4 ml/kgIBW; P = 0.990). In contrast, they showed higher respiratory rate (20 ± 5 vs. 18 ± 5 breaths/min; P = 0.028), minute ventilation (9.2 ± 3.0 vs. 7.9 ± 2.4 l/min; P = 0.011), tidal pleural pressure (8.1 ± 3.7 vs. 6.0 ± 3.1 cm H2O; P = 0.003), mechanical power ratio (2.4 ± 1.4 vs. 1.7 ± 1.5; P = 0.042), and lower partial pressure of alveolar oxygen/fractional inspired oxygen tension (174 ± 64 vs. 220 ± 95; P = 0.007). The mechanical power (area under the curve, 0.738; 95% CI, 0.636 to 0.839] P < 0.001), the mechanical power ratio (area under the curve, 0.734; 95% CI, 0.625 to 0.844; P < 0.001), and the pressure-rate index (area under the curve, 0.733; 95% CI, 0.631 to 0.835; P < 0.001) showed the highest areas under the curve.

Conclusions

In this COVID-19 cohort, tidal volume was similar in patients undergoing treatment escalation and in patients who did not; mechanical power, its ratio, and pressure-rate index were the variables presenting the highest association with the clinical outcome.

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What We Already Know about This Topic

What This Article Tells Us That Is New
Lung Injury Is Induced by Abrupt Increase in Respiratory Rate but Prevented by Recruitment Maneuver in Mild Acute Respiratory Distress Syndrome in Rats
Authors: Xavier Paulo Henrique , Fonseca Ana Carolina Fernandes , Gonçalves Leonardo Alves , de Sousa Giselle Cavalho , Silva Mariana Coelho da , Sacramento Raquel Ferreira de Magalhães , Samary Cynthia dos Santos , Medeiros Mayck , Cruz Fernanda Ferreira , Capelozzi Vera Luiza , Felix Nathane Satanna , Pelosi Paolo , Marini John J. , Rocco Patrícia Rieken Macêdo , Silva Pedro Leme
Published: December 2022

Background

Gradually changing respiratory rate (RR) during time to reduce ventilation-induced lung injury has not been investigated. The authors hypothesized that gradual, compared with abrupt, increments in RR would mitigate ventilation-induced lung injury and that recruitment maneuver before abruptly increasing RR may prevent injurious biologic impact.

Methods

Twenty-four hours after intratracheal administration of Escherichia coli lipopolysaccharide, 49 male Wistar rats were anesthetized and mechanically ventilated (tidal volume, 6 ml/kg; positive end-expiratory pressure, 3 cm H2O) with RR increase patterns as follows (n = 7 per group): (1) control 1, RR = 70 breaths/min for 2 h; (2) and (3) abrupt increases of RR for 1 and 2 h, respectively, both for 2 h; (4) shorter RR adaptation, gradually increasing RR (from 70 to 130 breaths/min during 30 min); (5) longer RR adaptation, more gradual increase in RR (from 70 to 130 breaths/min during 60 min), both for 2 h; (6) control 2, abrupt increase of RR maintained for 1 h; and (7) control 3, recruitment maneuver (continuous positive airway pressure, 30 cm H2O for 30 s) followed by control-2 protocol.

Results

At the end of 1 h of mechanical ventilation, cumulative diffuse alveolar damage scores were lower in shorter (11.0 [8.0 to 12.0]) and longer (13.0 [11.0 to 14.0]) RR adaptation groups than in animals with abrupt increase of RR for 1 h (25.0 [22.0 to 26.0], P = 0.035 and P = 0.048, respectively) and 2 h (35.0 [32.0 to 39.0], P = 0.003 and P = 0.040, respectively); mechanical power and lung heterogeneity were lower, and alveolar integrity was higher, in the longer RR adaptation group compared with abruptly adjusted groups; markers of lung inflammation (interleukin-6), epithelial (club cell secretory protein [CC-16]) and endothelial cell damage (vascular cell adhesion molecule 1 [VCAM-1]) were higher in both abrupt groups, but not in either RR adaptation group, compared with controls. Recruitment maneuver prevented the increase in VCAM-1 and CC-16 gene expressions in the abruptly increased RR groups.

Conclusions

In mild experimental acute respiratory distress syndrome in rats, gradually increasing RR, compared with abruptly doing so, can mitigate the development of ventilation-induced lung injury. In addition, recruitment maneuver prevented the injurious biologic impact of abrupt increases in RR.

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What We Already Know about This Topic

What This Article Tells Us That Is New
Novel Use of Olecranon Locking Plate With Achilles Allograft Augmentation for Fixation of Greater Trochanter Fractures After Total Hip Replacement
Authors: Smartt Anne A. , Sierra Rafael J.
Published: December 2022

Introduction:

The optimal fixation method for greater trochanteric fractures after a total hip replacement remains controversial. We present the surgical technique of a novel fixation method for greater trochanteric fractures with the use of an olecranon locking plate and Achilles tendon allograft augmentation.

Patients and Methods:

Five patients who had previously undergone a total hip arthroplasty for primary osteoarthritis were identified as presenting with displaced (>2 cm) greater trochanter fractures between 2017 and 2021. They underwent open reduction internal fixation of the greater trochanter with an olecranon locking plate and Achilles tendon allograft augmentation an average of 8 months after their index procedure (range: 2 to 17 mo), all performed by a single surgeon. All 5 patients were women, the mean age was 59 years (range: 54 to 69 y) and the mean follow-up time was 16.1 months (range: 5 to 41 mo).

Results:

All 5 patients reported improved pain levels and functional status after open reduction internal fixation. Four of the patients demonstrated maintenance of the position of the trochanteric fragment with the olecranon plate whereas one patient who was unable to comply with postoperative restrictions had a catastrophic failure of the fixation. One of 5 trochanteric bones showed clear evidence of radiographic union.

Conclusions:

Utilization of olecranon locking plates is well suited for fixation of a greater trochanter fracture as this technique allows for the capture of small comminuted fragments by the proximal curvature of the plate. In addition, this minimizes the concurrent use of metallic cables close to or within the effective joint space. Weight-bearing restrictions and stability are of the utmost importance in the postoperative time period.
Medial Oblique Eyelid Split Orbitotomy
Authors: Cruz Antonio Augusto V. , Guimarães Juliana A. , Akaishi Patricia M. , Milbratz-Moré Gherusa H. , Garcia Denny M.
Published: December 2022

Purpose:

The authors describe their experience with a variant of the split orbitotomy with a small medial oblique transmarginal incision for approaching a variety of lesions involving the superonasal aspect of the orbit.

Methods:

Retrospective review of medical records and clinical photographs of all patients who underwent an unilateral medial oblique incision to access various intraconal lesions abutting the superomedial quadrant of the orbit. The curvature of the medial contour of the operated and contralateral eyelids were expressed with Bézier functions and compared using the R-squared coefficient of determination (R2).

Results:

Twenty-three patients were submitted to this surgical technique for approaching various unilateral lesions on the superonasal quadrant of the orbit. Excellent cosmesis was achieved in all eyelids, with almost imperceptible scars, and no ptosis or retraction. There was no significant difference between the postoperative medial contour of the operated and the contralateral eyelid, with R2 ranging from 0.896 to 0.999, mean 0.971.

Conclusions:

The authors’ results show that the modified eyelid split approach provides a wide exposure of the superonasal quadrant of the orbit with no risk of eyelid dysfunctions or significant scars.