bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase Ib and Expansion Study of Gemcitabine,Nab-Paclitaxel, and Ficlatuzumab in Patients With Metastatic Pancreatic Cancer
Authors: Perez Kimberly , Chiarella Anna M , Cleary James M , Horick Nora , Weekes Colin , Abrams Thomas , Blaszkowsky Lawrence , Enzinger Peter , Giannakis Marios , Goyal Lipika , Meyerhardt Jeffrey A , Rubinson Douglas , Yurgelun Matthew B , Goessling Wolfram , Giantonio Bruce J , Brais Lauren , Germon Victoria , Stonely Danielle , Raghavan Srivatsan , Bakir Basil , Das Koushik , Pitarresi Jason R , Aguirre Andrew J , Needle Michael , Rustgi Anil K , Wolpin Brian M
Published: February 2023

Background

In preclinical pancreatic ductal adenocarcinoma (PDAC) models, inhibition of hepatocyte growth factor (HGF) signaling using ficlatuzumab, a recombinant humanized anti-HGF antibody, and gemcitabine reduced tumor burden.

Methods

Patients with previously untreated metastatic PDAC enrolled in a phase Ib dose escalation study with 3 + 3 design of 2 dose cohorts of ficlatuzumab 10 and 20 mg/kg administered intravenously every other week with gemcitabine 1000 mg/m2 and albumin-bound paclitaxel 125 mg/m2 given 3 weeks on and 1 week off. This was followed by an expansion phase at the maximally tolerated dose of the combination.

Results

Twenty-six patients (sex, 12 male:14 female; median age, 68 years [range, 49-83 years]) were enrolled, 22 patients were evaluable. No dose–limiting toxicities were identified (N = 7 pts) and ficlatuzumab at 20 mg/kg was chosen as the maximum tolerated dose. Among the 21 patients treated at the MTD, best response by RECISTv1.1: 6 (29%) partial response, 12 (57%) stable disease, 1 (5%) progressive disease, and 2 (9%) not evaluable. Median progression-free survival and overall survival times were 11.0 months (95% CI, 7.6-11.4 months) and 16.2 months (95% CI, 9.1 months to not reached), respectively. Toxicities attributed to ficlatuzumab included hypoalbuminemia (grade 3, 16%; any grade, 52%) and edema (grade 3, 8%; any grade, 48%). Immunohistochemistry for c-Met pathway activation demonstrated higher tumor cell p-Met levels in patients who experienced response to therapy.

Conclusion

In this phase Ib trial, ficlatuzumab, gemcitabine, and albumin-bound paclitaxel were associated with durable treatment responses and increased rates of hypoalbuminemia and edema.
Essential Entomology
Authors: McGavin George C. , Davranoglou Leonidas-Romanos , Lewington Richard
Published: February 2023

Insects are the most diverse multicellular organisms on Earth. With estimates of total insect species scaling to the order of several millions, it might be challenging for beginners to grasp the vastness of their diversity. This second edition of Essential Entomology offers the most comprehensive and up-to-date overview of insect orders available on the market. This book is written in simple language that is understandable to all and—as its title suggests—it is an essential read for anyone interested in entomology. Essential Entomology is addressed to undergraduate students in biology, agricultural, and forestry studies, as well as amateurs and citizen scientists of all levels. Besides the updated text, this new book boasts stunning macrophotographs of all insect orders by the world’s most renowned nature photographers. Each photo perfectly supplements Richard Lewington’s incredible illustrations. The first section of the book begins with an introduction to the Linnaean system of taxonomy, as well as basic concepts in insect morphology, physiology, and natural history. The second (and largest) section of the book introduces the reader to each insect order and reviews its diversity, identifiable characteristics, natural history, and evolutionary origin. To satisfy the curiosity of the interested reader, the end of each order provides an extensive bibliography. The final section reviews the main field techniques used for collecting insects, listing purpose and the pros and cons of each technique.
A History of Mathematical Impossibility
Authors: Lützen Jesper
Published: February 2023

Mathematical theorems stating that a problem cannot be solved using specific means are numerous. This book follows the history of such impossibility theorems from Greek antiquity through the early twentieth century. It reveals that many impossibility statements started out as meta-statements but ended up as mathematical theorems that were proved by mathematical methods. Until the nineteenth century, impossibility theorems were often considered of secondary interest compared with positive results. This changed during the nineteenth century and today impossibility results are among the most famous and popular theorems of mathematics. The book deals with some of the celebrated impossibility theorems in pure mathematics such as the quadrature of the circle, the duplication of the cube, the trisection of the angle, Fermat’s last theorem, the impossibility of proving the parallel postulate and Gödel’s theorem, as well as some theorems from applied mathematics such as Arrow’s impossibility theorem. Although an impossibility may sound as a negative result, impossibilities have in fact acted as a creative force in the history of mathematics, challenging mathematicians to circumvent the impossibility. The introduction of complex numbers is a case in point.
Left-Digit Bias at Lyft
Authors: List John A , Muir Ian , Pope Devin , Sun Gregory
Published: February 2023

Left-digit bias (or 99-cent pricing) has been discussed extensively in economics, psychology, and marketing. Despite this, we show that the rideshare company, Lyft, was not using a 99-cent pricing strategy prior to our study. Based on observational data from over 600 million Lyft sessions followed by a field experiment conducted with 21 million Lyft passengers, we provide evidence of large discontinuities in demand at dollar values. Approximately half of the downward slope of the demand curve occurs discontinuously as the price of a ride drops below a dollar value (e.g. $14.00 to $13.99). If our short-run estimates persist in the longer run, we calculate that Lyft could increase its profits by roughly $160M per year by employing a left-digit bias pricing strategy. Our results showcase the robustness of an important behavioral bias for a large, modern company and its persistence in a highly competitive market.
International Spillovers and Bailouts
Authors: Azzimonti Marina , Quadrini Vincenzo
Published: February 2023

We study how cross-country macroeconomic spillovers caused by sovereign default affect equilibrium bailouts. Because of portfolio diversification, the default of one country causes a macroeconomic contraction in other countries, which motivates a bailout. But why do creditor countries choose to bailout debtor countries instead of their own private sector? We show that this is because an external bailout could be cheaper than a domestic bailout. We also show that although anticipated bailouts lead to higher borrowing, they can be Pareto improving not only ex post (after a country has defaulted) but also ex ante (before the country chooses its debt).
Polysomnographic characterization of circadian blood pressure patterns in patients with obstructive sleep apnea
Authors: Pinilla Lucía , Benítez Iván D , Gracia-Lavedan Esther , Torres Gerard , Minguez Olga , Aguilà Maria , Targa Adriano , Dalmases Mireia , Mediano Olga , Masa Juan F , Masdeu Maria J , Barbé Ferran , Sánchez-de-la-Torre Manuel
Published: February 2023

We characterized the polysomnography (PSG) parameters associated with alterations in the circadian blood pressure (BP) pattern aiming to identify the main contributors to explain the nondipper profile in obstructive sleep apnea (OSA). This is an observational prospective-multicenter study that included participants referred to the sleep unit for suspected OSA. Following a PSG study, subjects with an apnea–hypopnea index (AHI) ≥5 events/hr were included. Two groups were established based on the 24-hr ambulatory blood pressure monitoring dipping ratio (DR; night/day BP ratio): dippers (DR ≤ 0.9) and nondippers (DR > 0.9). The cohort consisted of 299 patients: 131 (43.8%) dippers and 168 (56.2%) nondippers. A significant increase in the risk of presenting a nondipper BP pattern was found along with AHI gain [odds ratio (OR) (95% CI) = 1.71 (1.28 to 2.28)]. The best AHI cutoff for predicting nondipper status was 25.2 events/hr, increasing the OR (95% CI) to 3.50 (2.02 to 6.07). The hypopnea index [OR (95% CI) = 1.70 (1.27 to 2.26)], TSat90 [OR (95% CI) = 1.41 (1.06 to 1.87)], and respiratory arousal index [OR (95% CI) = 1.74 (1.30 to 2.34)] were individually associated with the risk of a nondipping pattern. Multivariate variable selection processes identified the respiratory arousal index as the most relevant risk factor for the nondipper profile, beyond classical clinical risk factors and usual PSG metrics.
Exploring the Value of Improvisational Theater in Medical Education for Advancing the Doctor–Patient Relationship and Health Equity
Authors: Rusiecki Jennifer M. , Orlov Nicola M. , Dolan James A. , Smith Michael P. , Zhu Mengqi , Chin Marshall H.
Published: February 2023

Purpose

Health care inequities persist, and it is difficult to teach health professions students effectively about implicit bias, structural inequities, and caring for patients from underrepresented or minoritized backgrounds. Improvisational theater (improv), where performers create everything in a spontaneous and unplanned manner, may help teach health professions trainees about advancing health equity. Core improv skills, discussion, and self-reflection can help improve communication; build trustworthy relationships with patients; and address bias, racism, oppressive systems, and structural inequities.

Method

Authors integrated a 90-minute virtual improv workshop using basic exercises into a required course for first-year medical students at University of Chicago in 2020. Sixty randomly chosen students took the workshop and 37 (62%) responded to Likert-scale and open-ended questions about strengths, impact, and areas for improvement. Eleven students participated in structured interviews about their experience.

Results

Twenty-eight (76%) of 37 students rated the workshop as very good or excellent, and 31 (84%) would recommend it to others. Over 80% of students perceived their listening and observation skills improved, and that the workshop would help them take better care of patients with experiences different than their own. Six (16%) students experienced stress during the workshop but 36 (97%) felt safe. Eleven (30%) students agreed there were meaningful discussions about systemic inequities. Qualitative interview analysis showed that students thought the workshop helped develop interpersonal skills (communication, relationship building, empathy); helped personal growth (insights into perception of self and others, ability to adapt to unexpected situations); and felt safe. Students noted the workshop helped them to be in the moment with patients and respond to the unexpected in ways more traditional communication curricula have not. The authors developed a conceptual model relating improv skills and equity teaching methods to advancing health equity.

Conclusions

Improv theater exercises can complement traditional communication curricula to advance health equity.
A Model to Improve Care and Enhance the Physician–Patient Relationship for Hospitalized Patients With Opioid Use Disorder
Authors: Ari Mim , Murray John , Dickson Sarah , Kerins Angela , Weyer George
Published: February 2023

Problem

Opioid-related morbidity and mortality continues to accelerate, with increasing acute care events for opioid-related causes. Most patients do not receive evidence-based treatment for opioid use disorder (OUD) during acute hospitalizations despite this being an invaluable moment to initiate substance use treatment. Inpatient addiction consult services can bridge this gap and improve patient engagement and outcomes, but varying models and approaches are needed to match institutional resources.

Approach

To improve care for hospitalized patients with OUD, a work group was formed at the University of Chicago Medical Center in October 2019. An OUD consult service, run by generalists, was created as part of a series of process improvement interventions. Important collaborations with pharmacy, informatics, nursing, physicians, and community partners have occurred over the last 3 years.

Outcomes

The OUD consult service completes 40–60 new inpatient consults monthly. Between August 2019 and February 2022, the service completed 867 consults from across the institution. Most consult patients were started on medications for opioid use disorder (MOUD), and many received MOUD and naloxone at discharge. Patients who were treated by our consult service experienced lower 30-day and 90-day readmission rates compared with patients who did not receive a consult. Length of stay for patients receiving a consult was not increased.

Next Steps

Adaptable models of hospital-based addiction care are needed to improve care for hospitalized patients with OUD. Continued work to reach a higher percentage of hospitalized patients with OUD and to improve linkage to care with community collaborators are important steps to strengthen the care received by individuals with OUD in all clinical departments.
Thumb Carpometacarpal Stabilization With a Dorsal Capsule Repair Augmented With an Internal Brace
Authors: Kronlage Steven C. , Whitaker Edward Alex
Published: February 2023

Optimal surgical treatment of first carpometacarpal joint instability remains a subject of debate. Consensus on thumb carpometacarpal stability originating with the dorsoradial ligamentous complex has shifted reconstruction techniques towards stabilization dorsally. We describe a dorsal stabilization technique with internal brace augmentation of the dorsoradial ligamentous complex. A single fellowship-trained hand surgeon treated 10 women, average age 34 years (range, 21 to 52 y) and 1 man, age 34 years, between 2019 and 2022. Average patient follow-up was 2 years. Patient satisfaction was high. Further trials are needed to determine whether the procedure will prevent or delay the presentation of thumb carpometacarpal arthrosis.
Simultaneous Inhibition of PI3Kgamma and PI3Kdelta Deteriorates T-cell Function With Implications for Chronic Lymphocytic Leukemia
Authors: Faehling Sebastian , Coelho Mariana , Floerchinger Alessia , Schneider Christof , Stilgenbauer Stephan , Lichter Peter , Seiffert Martina , Roessner Philipp M.
Published: February 2023

Chronic lymphocytic leukemia (CLL) is a common and incurable B-cell malignancy. Recent therapeutic approaches that target the B-cell receptor signaling pathway include inhibition of phosphatidylinositol-3-kinase (PI3K). The PI3K isoform delta is constitutively active in CLL, making it an attractive therapeutic target. However, the expression of PI3K isoforms is not exclusive to leukemic cells, as other immune cells in the tumor microenvironment also rely on PI3K activity. Subsequently, therapeutic inhibition of PI3K causes immune-related adverse events (irAEs). Here, we analyzed the impact of the clinically approved PI3Kδ inhibitors idelalisib and umbralisib, the PI3Kγ inhibitor eganelisib, and the dual-γ and -δ inhibitor duvelisib on the functional capacity of T cells. All investigated inhibitors reduced T-cell activation and proliferation in vitro, which is in line with PI3K being a crucial signaling component of the T-cell receptor signaling. Further, dual inhibition of PI3Kγ and PI3Kδ showed strong additive effects suggesting a role also for PI3Kγ in T cells. Extrapolation of this data to a clinical setting could provide an explanation for the observed irAEs in CLL patients undergoing treatment with PI3K inhibitors. Consequently, this highlights the need for a close monitoring of patients treated with PI3K inhibitors, and particularly duvelisib, due to their potentially increased risk of T-cell deficiencies and associated infections.
Predicting Delayed Shock in Multisystem Inflammatory Disease in Children
Authors: Levine Deborah A. , Uy Vincent , Krief William , Bornstein Cara , Daswani Dina , Patel Darshan , Kriegel Marni , Jamal Nazreen , Patel Kavita , Liang Tian , Arroyo Alexander , Strother Christopher , Lim Czer Anthoney , Langhan Melissa L. , Hassoun Ameer , Chamdawala Haamid , Kaplan Carl Philip , Waseem Muhammad , Tay Ee Tein , Mortel David , Sivitz Adam B. , Kelly Christopher , Lee Horton James , Qiu Yuqing , Gorelik Mark , Platt Shari L. , Dayan Peter
Published: February 2023

Objectives

Patients with multisystem inflammatory disease in children (MIS-C) are at risk of developing shock. Our objectives were to determine independent predictors associated with development of delayed shock (≥3 hours from emergency department [ED] arrival) in patients with MIS-C and to derive a model predicting those at low risk for delayed shock.

Methods

We conducted a retrospective cross-sectional study of 22 pediatric EDs in the New York City tri-state area. We included patients meeting World Health Organization criteria for MIS-C and presented April 1 to June 30, 2020. Our main outcomes were to determine the association between clinical and laboratory factors to the development of delayed shock and to derive a laboratory-based prediction model based on identified independent predictors.

Results

Of 248 children with MIS-C, 87 (35%) had shock and 58 (66%) had delayed shock. A C-reactive protein (CRP) level greater than 20 mg/dL (adjusted odds ratio [aOR], 5.3; 95% confidence interval [CI], 2.4–12.1), lymphocyte percent less than 11% (aOR, 3.8; 95% CI, 1.7–8.6), and platelet count less than 220,000/uL (aOR, 4.2; 95% CI, 1.8–9.8) were independently associated with delayed shock. A prediction model including a CRP level less than 6 mg/dL, lymphocyte percent more than 20%, and platelet count more than 260,000/uL, categorized patients with MIS-C at low risk of developing delayed shock (sensitivity 93% [95% CI, 66–100], specificity 38% [95% CI, 22–55]).

Conclusions

Serum CRP, lymphocyte percent, and platelet count differentiated children at higher and lower risk for developing delayed shock. Use of these data can stratify the risk of progression to shock in patients with MIS-C, providing situational awareness and helping guide their level of care.
The Utility of Smartphone-Based Thermal Imaging in the Management and Monitoring of Microvascular Flap Procedures
Authors: Hudson Todd , Hogue Elizabeth , Mullner Donna , Herrera Fernando , Scomacao Isis
Published: February 2023

Background

Smartphone-based thermal imaging (SBTI) has been reported in the literature to be an easy-to-use, contactless, cost-friendly alternative to standard imaging modalities in identifying flap perforators, monitoring flap perfusion, and detecting flap failure. Our systematic review and meta-analysis aimed to evaluate SBTI's accuracy in perforator identification and secondarily evaluate SBTI's utility in flap perfusion monitoring as well as ability to predict flap compromise, failure, and survival.

Methods

Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, a systematic review was performed using PubMed from inception to 2021. Articles were uploaded into Covidence and, following duplicate deletion, were initially screened for use of SBTI in flap procedures through title and abstract screening followed by full-text review. The following data points, if provided, were extracted from each included study: study design, number of patients, patient demographics, perforator number and location, flap number and location, room temperature, cooling method, imaging distance, time from cloth removal, primary (SBTI's accuracy in perforator identification), and secondary outcomes (prediction of flap compromise/failure/survival and cost analysis). Meta-analysis was performed using RevMan v.5.

Results

The initial search yielded 153 articles. Eleven applicable studies with a total of 430 flaps from 416 patients were ultimately included. The SBTI device assessed in all included studies was FLIR ONE. Four studies assessed the SBTI's perforated detection ability and were included in meta-analysis. Smartphone-based thermal imaging correctly identified 378 (93.3%; n = 405) perforators, and computed tomography angiography (CTA) correctly identified 402 (99.2%; n = 402), although in one study SBTI found additional perforators not detected on CTA. A random-effects model was used (I
2 = 65%), and no significant difference in perforator detection ability was found between SBTI and CTA (P = 0.27).

Conclusions

This systematic review and meta-analysis supports SBTI as user- and cost-friendly ($229.99), contactless imaging modality with perforator detection ability comparable to current criterion-standard CTA. Postoperatively, SBTI outperformed Doppler ultrasound in early detection of microvascular changes causing flap compromise, allowing for prompt tissue salvage. With a minimal learning curve, SBTI seems to be a promising method of postoperative flap perfusion monitoring able to be used by all hospital ranks. Smartphone-based thermal imaging could thus increase flap monitoring frequency and lower complication rates, although further study is warranted.
High and Low Septal Strip Excision on Dorsal Preservation Rhinoplasty to Fix Septal Deviation
Authors: Öztürk Güncel
Published: February 2023

Rhinoplasty is one of the leading procedures among aesthetic and plastic surgery interventions. Dorsal hump and nasal deviation deformities are prevalent among the general population. Patients who have both dorsal hump and nasal deviation deformities can be considered challenging for rhinosurgeons. Dorsal preservation techniques are of great interest for obtaining better and more satisfactory aesthetic and functional results. Dorsal strip excision plays a considerable part in dorsal preservation techniques. In this study, the author defines a new method that includes excisions of low and high septal strips in the subdorsal area to straighten deviation in the lower part of the distal septum and fix it on the middle line. The present study was designed as retrospective. Sixty-nine patients met the inclusion and exclusion criteria, and their records were assessed (49 females and 20 males). The patients who were included in the study have undergone surgery with high and low septal strip excision through either push-down or let-down techniques. Patients were evaluated using the “Rhinoplasty Outcome Evaluation” (ROE) questionnaire before and 12 months after surgery. The follow-up period ranged between 12 and 20 months (median, 16.3 months). All procedures were performed by the same surgeon between October 1, 2018, and April 1, 2020. The ROE scores ranged between 82 and 100 points after 1 year. The initial median ROE score was 56.5, and it increased to 93.00 points 12 months after surgery (P < 0.001). Patient satisfaction was excellent in 88.76% of the included patients. The combination of let- and push-down methods with low to high septal strip excision resulted in favorable outcomes in patients who had concomitant hump and septal deviation deformities. This new approach presents a suitable and easy method to the surgeons who are interested in dorsal preservation rhinoplasty.
Incisional Release and Fat Grafting for the Surgical Management of Perioral Fibrosis in Scleroderma
Authors: Lagziel Tomer , Kawaji Qingwen , Hultman C. Scott
Published: February 2023

Introduction

Scleroderma (systemic sclerosis [SSc]) is a rare autoimmune, connective tissue disorder. Perioral fibrosis is a local cutaneous complication, negatively impacting functional capabilities and aesthetic satisfaction. Fat grafting has been postulated to aid in the management of SSc fibrosis thanks to stem cell enrichment. This technique's success has been demonstrated using different graft origin sites and different injection targets. We aim to demonstrate our SSc patients' success using abdominal fat and perioral target.

Methods

We queried our records for patients with preexisting SSc who underwent incisional release and fat grafting for perioral fibrosis from 2018 to 2021. For perioral release, a semisharp cannula was tunneled under the vermilion border into the vermilion and along the skin. For grafting, cannulas were used to infiltrate the fat with a retrograde filling technique in a radial-fanning manner. Their autoimmune diagnosis, anesthetic risk assessment, systemic disease complications, and degree of presenting symptoms were reviewed along with their postoperative outcomes.

Results

From 2018 to 2021, 16 patients diagnosed with SSc were treated with incisional release and fat grafting for the management of perioral fibrosis. Of the SSc patients, 8 presented with limited SSc, and 8 presented with diffuse SSc. The mean patient age was 54.31 years. All SSc patients presented with functional symptoms with the most common concern (n = 9) being “decreased mouth opening.” Other common complaints were “difficulty eating” (n = 3) or “difficulty drinking” (n = 2). Some patients (n = 11) also presented with cosmetic concerns with “perioral rhytids” being the most common (n = 6). The mean number of systemic complications, at the time of presentation, was 3.06. The mean anesthetic risk assessment was 2.44. The average amount of fat grafted intraoperatively was 14.89 mL. Two patients with SSc required regrafting. For one patient, this was part of the original treatment plan and for the other due to fat resorption. Patients who followed up reported improved functionality and were pleased aesthetically.

Conclusions

Patients with perioral fibrosis due to SSc can benefit from autologous fat grafting. Incisional release in combination with fat grafting can enhance procedure outcomes. This technique provides beneficial functional and aesthetic outcomes. Patients with both diffuse and limited disease are appropriate candidates for this procedure.
Discrepancies in Gender Representation Between Integrated and Independent Plastic Surgery Programs
Authors: Woodyard Kiersten C. , Hogan Elise , Dembinski Douglas , Lee Ermina , Effendi Maleeh , Gobble Ryan M.
Published: February 2023

Purpose

Despite increasing female representation in integrated plastic surgery training programs, independent programs have lower representation and slow improvement in female enrollment. Self-reported resident data were used to investigate trends of female representation in integrated and independent programs.

Methods

Data were collected from Accreditation Council of Graduate Medical Education resources of active residents' characteristics. Self-reported gender data were collected for integrated, independent, and general surgery programs from annual reports since 2009. χ2 analysis was conducted to compare female enrollment of integrated programs, independent programs, general surgery programs, and general surgery programs with matriculation-year adjustment.

Results

In 2008, 89 independent programs had nearly identical percentage of female enrollment with 30 integrated programs at 23.8% and 23.1%, respectively. Differences in representation between independent and integrated programs became significant in 2012, with independent programs demonstrating 25.1% female enrollment compared with 30.5% in integrated programs. This trend of higher female representation in integrated programs has persisted since 2012. To correct for preexisting disparity in general surgery programs, we compared female enrollment of independent programs with female enrollment of that class' general surgery matriculation-year 5 years earlier. In all examined years, general surgery still had proportionally higher female enrollment compared with independent programs, even with conservative 5-year matriculation adjustment.

Conclusions

Dramatic differences in female enrollment were found between integrated and independent programs, with representation in integrated programs rising more quickly. Adjustments for previous rates of female enrollment in general surgery did not yield explanation for low independent program enrollment. Increasing female representation in independent training models will continue to create a more diverse workforce.
Peer Review
Authors: Swanson Eric
Published: February 2023

Little information is available regarding how to review a plastic surgery manuscript. This vital responsibility ensures that publications meet an acceptable scientific standard. Thoughtful and thorough reviews are essential to protect patients and surgeons from unscientific practices and products. This discussion provides information for the reviewer, gained from the author's experience, including examples of a thorough review, likely to be useful to the editor, and a cursory one that is unhelpful.

The first consideration is relevance. Prerequisites for publication include institutional review board approval, disclosure of financial conflicts, and discussion of the regulatory status of devices. Particular attention is needed to check for conflicts of interest, which are endemic in plastic surgery today. In view of the common practice of using computer-generated imaging, reviewers need to be especially vigilant for inauthentic “photoshopped” photographs. Examples of published images that have been digitally altered are provided.

If data are available, it may be possible to check the statistical tests. Reviewers need to be aware of the practice of p-hacking. A quick literature search can identify relevant but unreferenced publications. The manuscript needs to be properly organized into sections. Minor points may be made regarding style. The study design and methodology need to be evaluated to be sure that the conclusions are well supported by data. Randomized studies are rarely feasible. Fortunately, well-done prospective observational studies in consecutive patients can be just as useful. Realistic complication rates are expected. Meta-analyses in plastic surgery are often subject to confounding variables. Comments should be available to the authors; confidential comments hidden from authors are discouraged. Like honesty, transparency is the best policy. Manuscripts should be evaluated solely for merit, not the identity of the author or institution. Timeliness of submission of the review is appreciated by authors.

Evidence-based medicine is concerned solely with the facts. The 2 basic criteria are a solid scientific basis and reliable evidence of efficacy. Reviewers need to keep an open mind. Studies that challenge the status quo are often the most valuable ones and are needed for the advancement of the specialty.
Replication of the natural selection of bad science
Authors: Kohrt Florian , Smaldino Paul E. , McElreath Richard , Schönbrodt Felix
Published: February 2023

This study reports an independent replication of the findings presented by Smaldino and McElreath (Smaldino, McElreath 2016
R. Soc. Open Sci.
3
, 160384 (
doi:10.1098/rsos.160384
)). The replication was successful with one exception. We find that selection acting on scientist’s propensity for replication frequency caused a brief period of exuberant replication not observed in the original paper due to a coding error. This difference does not, however, change the authors’ original conclusions. We call for more replication studies for simulations as unique contributions to scientific quality assurance.
A well-preserved ‘placoderm’ (stem-group Gnathostomata) upper jaw from the Early Devonian of Mongolia clarifies jaw evolution
Authors: Brazeau Martin D. , Yuan Haobo , Giles Sam , Jerve Anna L. , Zorig E. , Ariunchimeg Ya. , Sansom Robert S. , Atwood Robert C.
Published: February 2023

The origin of jaws and teeth remains contentious in vertebrate evolution. ‘Placoderms’ (Silurian-Devonian armoured jawed fishes) are central to debates on the origins of these anatomical structures. ‘Acanthothoracids’ are generally considered the most primitive ‘placoderms’. However, they are so far known mainly from disarticulated skeletal elements that are typically incomplete. The structure of the jaws—particularly the jaw hinge—is poorly known, leaving open questions about their jaw function and comparison with other placoderms and modern gnathostomes. Here we describe a near-complete ‘acanthothoracid’ upper jaw, allowing us to reconstruct the likely orientation and angle of the bite and compare its morphology with that of other known ‘placoderm’ groups. We clarify that the bite position is located on the upper jaw cartilage rather than on the dermal cheek and thus show that there is a highly conserved bite morphology among most groups of ‘placoderms’, regardless of their overall cranial geometry. Incorporation of the dermal skeleton appears to provide a sound biomechanical basis for jaw origins. It appears that ‘acanthothoracid’ dentitions were fundamentally similar in location to that of arthrodire ‘placoderms’, rather than resembling bony fishes. Irrespective of current phylogenetic uncertainty, the new data here resolve the likely general condition for ‘placoderms’ as a whole, and as such, ancestral morphology of known jawed vertebrates.
Genomic insights into schizophrenia
Authors: Owen Michael J.
Published: February 2023

Schizophrenia is a common, complex, heterogeneous psychiatric syndrome which can have profound impacts on affected individuals and imposes significant burdens on society. Despite intensive research, it has been challenging to understand basic mechanisms and to identify novel therapeutic targets. Given its high heritability and the complexity and inaccessibility of the human brain, much hope has been invested in the application of genomics as a route to better understanding. This work has identified many common and rare risk alleles and laid the foundations for a new generation of mechanistic studies. Genomics has also thrown new light on the relationship between schizophrenia and other psychiatric disorders and revealed its previously unappreciated aetiological relationship with childhood neurodevelopmental disorders, providing further evidence that it has its origins in disturbances of brain development. In addition, genomic findings suggest that the condition reflects fundamental disturbances in neuronal, and particularly synaptic, function that impact broadly on brain function, rather than being a disorder of specific brain regions and circuits. Finally, genomics has provided a plausible solution to the evolutionary paradox of how the condition persists in the face of high heritability and reduced fecundity.
Flextegrity simple cubic lattices
Authors: Boni Claudio , Royer-Carfagni Gianni
Published: February 2023

Flextegrity lattices are spatial grids composed of stiff segments kept in contact by compliant pre-tensioned tendons. The kinematic skeleton is sensible to the orientation of the segments, since their relative rotation produces the straining of the tendons to an amount that depends upon the angle of rotation and the shape of the pitch surfaces of the contact joints: these dictate the constitutive properties of the lattice in response to external actions. Two- and three-dimensional lattices are investigated, in which the contact pitch surfaces, obtained with axial-symmetric toothed conjugate profiles, mimic the kinematics of spheres, centred at the nodes of a simple cubic lattice, in pure rolling motion. The allowed mechanisms are discussed under infinitesimal deformation, to recognize possible eigenstress states in the lattice. The response under finite deformations is worked out for two-dimensional lattices under symmetric and asymmetric loading. The theoretical predictions are compared with experimental results on 3D-printed physical models. Possible extensions are discussed for lattices with segments of varying size, different arrangements and multi-stable contact joints. The flextegrity microstructure can represent a mesoscopic model for homogeneous crystals composed of non-pointwise molecules, but it could actually be manufactured in metamaterials with peculiar properties.
Stable isotope analyses of amino acids reveal the importance of aquatic resources to Mediterranean coastal hunter–gatherers
Authors: Fontanals-Coll Maria , Soncin Silvia , Talbot Helen M. , von Tersch Matthew , Gibaja Juan F. , Colonese André C. , Craig Oliver E.
Published: February 2023

Determining the degree to which humans relied on coastal resources in the past is key for understanding long-term social and economic development, as well as for assessing human health and anthropogenic impacts on the environment. Prehistoric hunter–gatherers are often assumed to have heavily exploited aquatic resources, especially those living in regions of high marine productivity. For the Mediterranean, this view has been challenged, partly by the application of stable isotope analysis of skeletal remains which has shown more varied coastal hunter–gatherer diets than in other regions, perhaps due to its lower productivity. By undertaking a more specific analysis of amino acids from bone collagen of 11 individuals from one of the oldest and best-known Mesolithic cemeteries in the Mediterranean, at El Collado, Valencia, we show that high levels of aquatic protein consumption were achieved. By measuring both carbon and nitrogen in amino acids, we conclude that some of the El Collado humans relied heavily on local lagoonal fish and possibly shellfish, rather than open marine species. By contrast to previous suggestions, this study demonstrates that the north-western coast of the Mediterranean basin could support maritime-oriented economies during the Early Holocene.
The emergence and shift in seasonality of Lyme borreliosis in Northern Europe
Authors: Goren Asena , Viljugrein Hildegunn , Rivrud Inger Maren , Jore Solveig , Bakka Haakon , Vindenes Yngvild , Mysterud Atle
Published: February 2023

Climate change has had a major impact on seasonal weather patterns, resulting in marked phenological changes in a wide range of taxa. However, empirical studies of how changes in seasonality impact the emergence and seasonal dynamics of vector-borne diseases have been limited. Lyme borreliosis, a bacterial infection spread by hard-bodied ticks, is the most common vector-borne disease in the northern hemisphere and has been rapidly increasing in both incidence and geographical distribution in many regions of Europe and North America. By analysis of long-term surveillance data (1995–2019) from across Norway (latitude 57°58′–71°08′ N), we demonstrate a marked change in the within-year timing of Lyme borreliosis cases accompanying an increase in the annual number of cases. The seasonal peak in cases is now six weeks earlier than 25 years ago, exceeding seasonal shifts in plant phenology and previous model predictions. The seasonal shift occurred predominantly in the first 10 years of the study period. The concurrent upsurgence in case number and shift in case timing indicate a major change in the Lyme borreliosis disease system over recent decades. This study highlights the potential for climate change to shape the seasonal dynamics of vector-borne disease systems.
CCDC15 localizes to the centriole inner scaffold and regulates centriole integrity and ciliogenesis
Authors: Arslanhan Melis D. , Steib Emmanuelle , Hamel Virginie , Guichard Paul , Firat-Karalar Elif Nur
Published: February 2023

Centrioles are evolutionarily conserved microtubule-based organelles critical to form centrosomes and cilia, which act as microtubule-organizing, signaling and motility centers. Biogenesis and maintenance of centrioles with proper number, size and architecture are crucial for their functions during development and physiology. Consequently, their deregulation causes developmental disorders and cancer. Although centriole number control has been extensively studied, less is known about how centrioles are maintained as stable structures with conserved size and architecture over successive cell divisions and upon ciliary and flagellar motility. Here, we addressed this question by identifying and characterizing new components of the centriole inner scaffold, a recently discovered centriolar sub-compartment critical for centriole size control and integrity. To this end, we generated proximity interactomes of Centrin-2 and POC5 and used them to define CCDC15 as a new centriolar protein that co-localizes and interacts with known inner scaffold proteins. Ultrastructure expansion microscopy analysis of CCDC15-depleted cells revealed its functions in centriole length control and integrity, resulting in defective ciliogenesis and Hedgehog signaling. Loss-of-function experiments also defined CCDC15 as a dual regulator for the recruitment of the inner scaffold protein POC1B and the distal SFI1/Centrin complex to the centrioles. Together, our findings uncovered new players and mechanisms of centriole architectural integrity and thereby, provide insights into diseases linked to centriolar defects.
SiHDA9 interacts with SiHAT3.1 and SiHDA19 to repress dehydration responses through H3K9 deacetylation in foxtail millet
Authors: Kumar Verandra , Singh Babita , Sharma Namisha , Muthamilarasan Mehanathan , Sawant Samir V. , Prasad Manoj
Published: February 2023

Drought stress affects the growth and productivity of plants, where C4plants can advantageously perceive and respond to the stress for their survival and reproduction. Epigenetic modifications play a prominent role in conferring drought tolerance in C4plants; however, the molecular links between histone modifiers and their regulation are unclear. In the present study, we performed a genome-wide H3K9ac enrichment in foxtail millet (Setaria italica) and analyzed their role in regulating the expression of drought-responsive genes. The presence of H3K9ac on these genes were identified through the comparative analysis of dehydration tolerant (cv. IC4) and sensitive (IC41) cultivars of foxtail millet. A histone deacetylase,SiHDA9, showed significant upregulation in the sensitive cultivar during dehydration stress.SiHDA9overexpression inArabidopsis thalianaconferred higher sensitivity to dehydration/drought stress than WT plants. We found that SiHDA9 physically interacts with SiHAT3.1 and SiHDA19. This complex is recruited through the SiHAT3.1 recognition sequence on the upstream of drought-responsive genes (SiRAB18, SiRAP2.4, SiP5CS2, SiRD22, SiPIP1;4, andSiLHCB2.3) to decrease H3K9 acetylation levels. The modulations in H3K9ac levels cause repression of gene expression and induce drought-sensitivity in the sensitive cultivar. Overall, the study provides mechanistic insights into SiHDA9-mediated regulation of drought stress response in foxtail millet.
Distinct roles of spinal commissural interneurons in transmission of contralateral sensory information
Authors: Laflamme Olivier D. , Markin Sergey N. , Banks Rachel , Zhang Ying , Danner Simon M. , Akay Turgay
Published: February 2023

Crossed reflexes (CR) are mediated by commissural pathways transmitting sensory information to the contralateral side of the body, but the underlying network is not fully understood. Commissural pathways coordinating the activities of spinal locomotor circuits during locomotion have been characterized in mice, but their relationship to CR is unknown. We show the involvement of two genetically distinct groups of commissural interneurons (CINs) described in mice, V0 and V3 CINs, in the CR pathways. Our data suggest that the exclusively excitatory V3 CINs are directly involved in the excitatory CR, and show that they are essential for the inhibitory CR. In contrast, the V0 CINs, a population that includes excitatory and inhibitory CINs, are not directly involved in excitatory or inhibitory CRs but down-regulate the inhibitory CR. Our data provide insights into the spinal circuitry underlying CR in mice, describing the roles of V0 and V3 CINs in CR.
A cell-type-specific multi-protein complex regulates expression of Cyclin B protein inDrosophilamale meiotic prophase
Authors: Baker Catherine C. , Gallicchio Lorenzo , Parsanian Lucineh , Taing Emily , Tam Cheuk , Fuller Margaret T.
Published: February 2023

During meiosis, germ cell and stage-specific components impose additional layers of regulation on the core cell cycle machinery to set up an extended G2 period termed meiotic prophase. InDrosophilamales, meiotic prophase lasts 3.5 days, during which spermatocytes turn up expression of over 3000 genes and grow 25-fold in volume. Previous work showed that the core cell cycle regulator Cyclin B (CycB) is subject to translational repression in immatureDrosophilaspermatocytes, mediated by the RNA-binding protein Rbp4 and its partner Fest. Here we show that another spermatocyte-specific protein, Lut, is required for translational repression ofcycBin an 8-hour window just before spermatocytes are fully mature. In males mutant forrbp4orlut, spermatocytes enter and exit the meiotic divisions 6-8 hours earlier than in wild-type. In addition, we show that spermatocyte-specific isoforms of Syncrip (Syp) are required for expression of CycB protein and normal entry into the meiotic divisions. Both Lut and Syp interact with Fest in an RNA-independent manner. Thus a complex of spermatocyte-specific regulators choreograph the timing of expression of CycB protein during male meiotic prophase.

SUMMARY STATEMENT

Expression of a conserved cell cycle component, Cyclin B, is regulated by multiple mechanisms in theDrosophilamale germline to dictate the correct timing of meiotic division.
Interpersonal early adversity demonstrates dissimilarity from early socioeconomic disadvantage in the course of human brain development: A meta-analysis
Authors: Vannucci Anna , Fields Andrea , Hansen Eleanor , Katz Ariel , Kerwin John , Tachida Ayumi , Martin Nathan , Tottenham Nim
Published: February 2023

It has been established that early-life adversity impacts brain development, but the role of development itself has largely been ignored. We take a developmentally-sensitive approach to examine the neurodevelopmental sequelae of early adversity in a preregistered meta-analysis of 27,234 youth (birth to 18-years-old), providing the largest group of adversity-exposed youth to date. Findings demonstrate that early-life adversity does not have an ontogenetically uniform impact on brain volumes, but instead exhibits age-, experience-, and region-specific associations. Relative to non-exposed comparisons, interpersonal early adversity (e.g., family-based maltreatment) was associated with initially larger volumes in frontolimbic regions until ~10-years-old, after which these exposures were linked to increasingly smaller volumes. By contrast, socioeconomic disadvantage (e.g., poverty) was associated with smaller volumes in temporal-limbic regions in childhood, which were attenuated at older ages. These findings advance ongoing debates regarding why, when, and how early-life adversity shapes later neural outcomes.