Assessing tuberculosis in the skeleton with the use of decision tree analysis.

Diagnosis of specific infectious diseases in the skeleton is often difficult and relies on expert opinion. Statistics is not often used as a tool to assist in such diagnoses, and therefore this study aimed at employing data mining and machine learning in the form of decision tree analysis to aid in recognizing tuberculosis (TB) in skeletal remains and find patterns of skeletal involvement. The sample included 387 modern South African individuals (n = 207 individuals known to have died of TB and n = 180 as a control group) which were scored for the presence or absence of 21 skeletal lesions documented to be associated with TB. A pruned decision tree classification analysis was done to detect significant patterns and associations between variables which produced a model with a moderate classification rate based on four of the variables. As expected, vertebral changes were selected first, followed by rib, acetabular and lastly cranial changes. As a proof of concept, it was shown that machine learning was able to identify patterns of changes in TB skeletons versus a control group. However, further investigation into the use of machine learning in assessing skeletal changes associated with specific diseases is needed.

Design, synthesis and biological evaluation of novel DCLK1 inhibitor containing purine skeleton for the treatment of pancreatic cancer.

Pancreatic cancer is a highly lethal form of malignancy that continues to pose a significant and unresolved health challenge. Doublecortin-like kinase 1 (DCLK1), a serine/threonine kinase, is found to be overexpressed in pancreatic cancer and holds promise as a potential therapeutic target for this disease. However, few potent inhibitors have been reported currently. Herein, a series of novel purine, pyrrolo [2,3-d]pyrimidine, and pyrazolo [3,4-d] pyrimidine derivatives were designed, synthesized, and evaluated their biological activities in vitro. Among them, compound I-5 stood out as the most potent compound with strong inhibitory activity against DCLK1 (IC50 = 171.3 nM) and remarkable antiproliferative effects on SW1990 cell lines (IC50 = 0.6 µM). Notably, I-5 exhibited higher in vivo antitumor potency (Tumor growth inhibition value (TGI): 68.6 %) than DCLK1-IN-1 (TGI: 24.82 %) in the SW1990 xenograft model. The preliminary mechanism study demonstrated that I-5 not only inhibited SW1990 cell invasion and migration, but also decreased the expression of prominin-1 (CD133) and cluster of differentiation 44 (CD44), which are considered as differentiation markers for SW1990 stem cells. All the results indicated that I-5, a novel DCLK1 inhibitor, shows promise for further investigation in the treatment of pancreatic cancer.

Discovery of estrogen receptor α targeting caged hypoxia-responsive PROTACs with an inherent bicyclic skeleton for breast cancer treatment.

In view of the potential off-target effects of antitumor drugs, including proteolysis targeting chimera (PROTAC), certain toxic effects may be caused in normal tissues. Herein, based on the characteristics of the tumor microenvironment, we reported the first estrogen receptor α (ERα) targeting hypoxia-responsive PROTACs in order to improve their safety in breast cancer treatment by introducing two hypoxia-activated groups, nitroimidazole and nitrobenzene, into the ER ligand or E3 ligand of an active PROTAC, which has certain cytotoxicity in normal cells. Bioactivity studies showed that these hypoxia-responsive PROTACs exhibited excellent hypoxic responsiveness and ERα degradation activity under hypoxic conditions, and thus improved the toxic effects of the active PROTAC in normal cells. It is expected that our caged compounds provide a new strategy for precise functional control of PROTAC drugs for breast cancer treatment.

A rare femoral heterotopic bone formation in a 14th-19th century female skeleton from Constância (Portugal).

OBJECTIVE: This paper aims to: (1) document a rare femoral heterotopic ossification (HO), and (2) discuss its aetiology and impact on the individual's locomotion and daily living activities. MATERIALS: Adult female skeleton (SG.14-SK.7) from the village of Constância (Portugal), and dated from the 14th-19th centuries CE. METHODS: The biological profile and the macroscopic analysis of the bone changes were assessed using standardized methods. RESULTS: The macroscopic analysis revealed a large bony mass (8 cm length) located immediately inferior to the small trochanter of the right femur. The lesion exhibited a compact, tubular appearance located at the site of attachment of the pectineus muscle. No signs of bone fracture were observed. CONCLUSIONS: The morphology of the SG.14-SK.7 femoral lesion is compatible with a probable case of myositis ossificans traumatica (MOT), secondary to acute trauma of the pectineus muscle. The underlying trauma episode, such as random accidental and/or occupation-related injury, is unknown. However, it is highly possible that this self-limiting condition significantly impaired the individual's daily life and mobility. SIGNIFICANCE: Evidence of severe acute muscle trauma is a rare finding compared with HO secondary to bone trauma and other minor muscle injuries. Moreover, no cases of MOT affecting the pectineus muscle have been reported in the paleopathological literature to date. LIMITATIONS: Although unlikely, a case of neurogenic or burn-related HO cannot be completely disregarded. It was not possible to undertake radiography as part of this study. SUGGESTIONS FOR FURTHER RESEARCH: The use of imaging techniques to complement the paleopathological description is advised.

Case Report: A Giant Epignathus with a Well-Developed Skeleton of Head and Neck.

Epignathus is an extremely rare teratoma found in the oral cavity or oropharyngeal region of newborns, whose pathogenesis is poorly understood. We describe a giant epignathus arising from the oropharynx in a newborn. The giant tumor completely obstructed the airway of the newborn resulting in death. Histological and radiological examination of the tumor reveals the presence of a remarkably well-developed skeleton of the head and neck. A row of teeth, the axis and atlas, thyroid and salivary glands, trachea, and cerebral tissue are all detected within the tumor. These findings suggest that the epignathus is fetus-in-fetu which is considered a type 0 germ cell tumor in accordance with current literature.

The association between skeletal lesions and tuberculosis in a pre-antibiotic South African sample.

OBJECTIVE: This study assessed the sensitivity and specificity of skeletal lesions to accurately diagnose TB in a pre-antibiotic South African skeletal sample. MATERIALS: A total of 435 skeletons of individuals who died before 1950 from the Raymond A. Dart Collection of Human Skeletons. 176 died of TB, 109 died of other pulmonary diseases, and 150 died of other causes. METHODS: The presence / absence of 23 skeletal lesions were assessed for differences in frequency between groups. Sensitivities and specificities were calculated and compared to Dangvard Pedersen et al. (2019). RESULTS: Lesions on the ventral surface of thoracic and lumbar vertebral bodies were observed significantly more often in TB and pulmonary cases than in other cause of death group and yielded a 55% probability of a true TB diagnosis, if observed. An association between skeletal lesions and TB was found for rib and vertebral lesions. CONCLUSIONS: The results suggest that even when not documented to have died of TB, TB-related changes are observed in many individuals in a South African skeletal sample, indicating that they may have been infected with the disease. SIGNIFICANCE: The study provides information that can assist palaeopathologists in making inferences about the prevalence of TB in past populations. LIMITATIONS: Sample sizes were small, and the inclusion of a pulmonary disease group may have confounded the results. SUGGESTIONS FOR FURTHER RESEARCH: The selection of a control group without any possible contact with TB may improve the results and should be investigated.

Lumbosacral tuberculosis, a rare manifestation of Pott's disease - How identified human skeletons from the pre-antibiotic era can be used as reference cases to establish a palaeopathological diagnosis of tuberculosis.

The macromorphological examination of identified human osteological collections from the pre-antibiotic era (e.g., Terry Collection) can provide invaluable information about the skeletal manifestations of tuberculosis (TB) in individuals who did not receive pharmaceutical therapy. With analysis of such collections, new diagnostic criteria for TB can be recognised which can be used in palaeopathological interpretation. The aim of our paper is to provide a reference and aid for the identification of TB in past populations by demonstrating and discussing in detail the vertebral alterations indicative of one of its rare skeletal manifestations, lumbosacral TB. These changes were detected in two individuals from the Terry Collection (Terry No. 760 and Terry No. 1093). These two case studies furnish palaeopathologists with a stronger basis for diagnosing lumbosacral TB in skeletons which exhibit similar vertebral lesions from osteoarchaeological series. To illustrate this, an archaeological case from Hungary (KK146) is also presented, displaying vertebral alterations resembling that of the two cases from the Terry Collection. Through the demonstrated case studies, we can derive a better insight into the disease experience of people who lived in the past and suffered from TB.

Prediction of microvascular invasion in hepatocellular carcinoma with expert-inspiration and skeleton sharing deep learning.

BACKGROUND AND AIMS: Radiological prediction of microvascular invasion (MVI) of hepatocellular carcinoma (HCC) is essential but few models were clinically implemented because of limited interpretability and generalizability. METHODS: Based on 2096 patients in three independent HCC cohorts, we established and validated an MVI predicting model. First, we used data from the primary cohort to train a 3D-ResNet network for MVI prediction and then optimised the model with "expert-inspired training" for model construction. Second, we implemented the model to the other two cohorts using three implementation strategies, the original model implementation, data sharing model implementation and skeleton sharing model implementation, the latter two of which used part of the cohorts' data for fine-tuning. The areas under the receiver operating characteristic curve (AUCs) were calculated to compare the performances of different models. RESULTS: For the MVI predicting model, the AUC of the expert-inspired model was 0.83 (95% CI: 0.77-0.88) compared to 0.54 (95% CI: 0.46-0.62) of model before expert-inspiring. Taking this model as an original model, AUC on the second cohort was 0.76 (95% CI: 0.67-0.84). The AUC was improved to 0.83 (95% CI: 0.77-0.90) with the data-sharing model, and further improved to 0.85 (95% CI: 0.79-0.92) with the skeleton sharing model. The trend that the skeleton sharing model had an advantage in performance was similar in the third cohort. CONCLUSIONS: We established an expert-inspired model with better predictive performance and interpretability than the traditional constructed model. Skeleton sharing process is superior to data sharing and direct model implementation in model implementation.

Correlation between whole skeleton dual energy CT calcium-subtracted attenuation and bone marrow infiltration in multiple myeloma.

OBJECTIVES: Objective evaluation of the extent of skeletal marrow involvement in multiple myeloma remains a clinical gap for CT. We aimed to develop a quantitative segmentation pipeline for dual energy CT and to assess whether quantified whole skeleton calcium-subtracted attenuation values correlate with biopsy-derived bone marrow infiltration in multiple myeloma. METHODS: Consecutive prospective patients with suspected/established myeloma underwent dual source CT from the skull vertex to proximal tibia. Whole skeleton segmentation was performed for 120 kVp-equivalent images as follows: following Hounsfield unit (HU) thresholding, a Chan-Vese morphological operation was implemented to generate a whole skeleton segmentation mask. This mask was then applied to corresponding whole skeleton material decomposition calcium-subtracted maps, generating whole skeleton HU values. Associations with biopsy-derived bone marrow plasma cell infiltration percentage were assessed with Spearman's rank correlation; significance was at 5%. RESULTS: 21 patients (12 females; median (IQR) 67 (61, 73) years) were included; 16 patients had osteolytic bone lesions; 15 patients underwent bone marrow biopsy. Segmentation and quantification were feasible in all patients. Median (IQR) of the average skeletal calcium-subtracted attenuation was -59.9 HU (-66.3, -51.8HU). There was a positive correlation with bone marrow plasma cell infiltration percentage (Spearman's rho: + 0.79, p < 0.001). CONCLUSION: Whole skeleton calcium-subtracted attenuation is associated with the degree of bone marrow infiltration by plasma cells, providing an objective measure of marrow involvement with the potential to allow earlier detection of disease.

Divalent metal cations stimulate skeleton interoception for new bone formation in mouse injury models.

Bone formation induced by divalent metal cations has been widely reported; however, the underlying mechanism is unclear. Here we report that these cations stimulate skeleton interoception by promoting prostaglandin E2 secretion from macrophages. This immune response is accompanied by the sprouting and arborization of calcitonin gene-related polypeptide-α+ nerve fibers, which sense the inflammatory cue with PGE2 receptor 4 and convey the interoceptive signals to the central nervous system. Activating skeleton interoception downregulates sympathetic tone for new bone formation. Moreover, either macrophage depletion or knockout of cyclooxygenase-2 in the macrophage abolishes divalent cation-induced skeleton interoception. Furthermore, sensory denervation or knockout of EP4 in the sensory nerves eliminates the osteogenic effects of divalent cations. Thus, our study reveals that divalent cations promote bone formation through the skeleton interoceptive circuit, a finding which could prompt the development of novel biomaterials to elicit the therapeutic power of these divalent cations.

Human skeletal remains analysis rom pallemalala shell midden in Southern Sri Lanka / Análisis de restos óseos humanos del vertedero de conchas de pallemalala en el sur de Sri Lanka

SUMMARY: Sri Lanka, an island off the tip of the Southeast of the Indian subcontinent processes the earliest skeletal evidence of anatomically modern Homo sapiens (37,000 B.P.) and the best human skeletal record sequence in the South Asian region. Adding another to the list, the skeletal remains, which belong to Mesolithic culture were found at Pallemalala shell midden in Southern Sri Lanka during scientific archaeological exploration by Postgraduate Institute of Archaeology, University of Kelaniya. Sri Lanka. The aim of the study was to determine the minimum number of human individuals, age, sex, and pathological conditions related to the ancient Pallemalala commiunity. For the primary analysis, 426 bone fragments were available. Out of those, 233 bones were identified as human bones which represent 7 minimum number of individuals. The rest of the collection comprises some animal bones and shell species. The community was predominated by the female population. The identified age categories were around 20 years, between 35-45 years, and over 45 years. The encountered pathological lesions were bone thickening, alveolar resorption, dental abscesses, dental caries, antemorterm tooth loss, calculus deposits and brown colour stains on teeth. Regarding the dietary pattern, it was evident that their diet may have consisted of coarse foodstuffs with an extremely basic dietary chemistry.

RESUMEN: Sri Lanka es una isla en la punta del sureste del subcontinente indio que procesa la evidencia esquelética más antigua del Homo sapiens anatómicamente moderno (37.000 AP) y la mejor secuencia de registros esqueléticos humanos en la región del sur de Asia. Agregando otro elemento a la lista, los restos óseos, que pertenecen a la cultura mesolítica, se encontraron en el vertedero de conchas de Pallemalala en el sur de Sri Lanka durante la exploración arqueológica científica realizada por el Instituto de Postgrado de Arqueología de la Universidad de Kelaniya, Sri Lanka. El objetivo del estudio fue determinar el número mínimo de individuos humanos, edad, sexo y condiciones patológicas relacionadas con la antigua comunidad Pallemalala. Para el análisis se dispuso de 426 fragmentos óseos. De esos, 233 huesos fueron identificados como huesos humanos que representan un número mínimo de 7 individuos. El resto de la colección se componía de algunos huesos de animales y especies de conchas. La comunidad estaba dominada por la población femenina. Las categorías de edad identificadas fueron alrededor de 20 años, entre 35-45 años y mayores de 45 años. Las lesiones patológicas encontradas fueron engrosamiento óseo, reabsorción alveolar, abscesos dentales, caries dental, pérdida de dientes antemortem, depósitos de cálculo y manchas de color marrón en los dientes. En cuanto al patrón dietético, era evidente que su dieta pudo haber consistido en alimentos toscos con una química dietética extremadamente básica.

Significant Asymmetry of the Bilateral Upper Extremities of a Skeleton Excavated from the Mashiki-Azamabaru Site, Okinawa Island, Japan.

The human skeleton of a young adult male with marked asymmetry of the bilateral upper extremities was excavated from the Mashiki-Azamabaru site (3000-2000 BCE) on the main island of Okinawa in the southwestern archipelago of Japan. The skeleton was buried alone in a corner of the cemetery. In this study, morphological and radiographic observations were made on this skeleton, and the pathogenesis of the bone growth disorder observed in the left upper limb was discussed. The maximum diameter of the midshaft of the humerus was 13.8 mm on the left and 21.2 mm on the right. The long bones comprising the left upper extremity lost the structure of the muscle attachments except for the deltoid tubercle of the humerus. The bone morphology of the right upper extremity and the bilateral lower extremities was maintained and was close to the mean value of females from the Ohtomo site in northwestern Kyushu, Japan, during the Yayoi period. It is assumed that the anomalous bone morphology confined to the left upper extremity was secondary to the prolonged loss of function of the muscles attached to left extremity bones. In this case, birth palsy, brachial plexus injury in childhood, and acute grey matter myelitis were diagnosed. It was suggested that this person had survived into young adulthood with severe paralysis of the left upper extremity due to injury or disease at an early age.

[MRI of the axial skeleton for evaluation of prostate cancer extent in french Guyana]. / IRM du squelette axial pour le bilan du cancer de prostate en Guyane française.

INTRODUCTION: Spread evaluation of Prostate Cancer (PC) in French Guyana is bothered by the lack of bone scintigraphy. The availability of 4 MRI allows to develop alternatives using Axial Skeleton MRI (AS MRI). We report the related results. MATERIAL: AS MRI was done in patients with diagnosis of high risk PC: PSA>=10ng/ml and/or Gleason Score>=7 (predominant Gleason grade 4) and/or clinical T2b and/or T2b/T3 MRI and/or >50% positive biopsies. AS MRI was including spine, pelvis and skull assessement.The results were systematically compared to the clinical, biological and biopsy features. RESULTS: Amongst 163 AS MRI performed, 30 were positive and 133 negative. Of these 133 patients, 60 were submited to radical prostatectomy with or without lymphadenectomy. In these 133 patients with negative AS MRI, median PSA was 11ng/ml (1-51) and 27 (20,3%) had PSA>20ng/ml. In patients with positive AS MRI, only 1 had PSA<20ng/ml and predominant Gleason grade 3. CONCLUSION: Our study shows that AS MRI assessement is especially usefull in patients who are most likely to have bone metastasis that is to say those with PSA>20ng/ml and/or predominant Gleason grade 4. LEVEL OF EVIDENCE: 3.

Chordoma: Current status, problems, and future directions.

Chordoma is a rare tumor that occurs along the axial spine in pediatrics and adults, with an incidence of approximately 350 cases per year in the United States. While typically described as slow-growing, many patients will eventually develop loco-regional relapse or metastatic disease with few treatment options. Despite numerous efforts over the last 10+ years, effective treatments for patients are lacking. As subtypes of chordoma are identified and described in more detail, further knowledge regarding the natural history of each type, tumor location, age differences, genomic variability, and an overall better understanding of chordoma may be the key to developing meaningful clinical trials and effective therapies for patients with chordoma.

An intrafamilial phenotypic variability in Ellis-Van Creveld syndrome due to a novel 27 bps deletion mutation.

Ellis-van Creveld (EvC) syndrome is an autosomal recessive disease, characterized by ectodermal, skeletal, and cardiac anomalies. We report intrafamilial phenotypic variability in three new EvC syndrome cases. Affected males in this study showed only ectodermal abnormalities, whereas an affected female showed the classical presentation of EvC Syndrome, including bilateral postaxial polydactyly of hands and feet, and congenital heart defects. Whole exome sequencing was performed to identify the causative variant, followed by validation and segregation analysis using Sanger sequencing. A homozygous deletion variant (c.731_757del) was identified in exon 6 of the EVC gene (NM_153717.2). The identified variant is considered to be the most likely candidate variant for the EvC syndrome in the family based on previous reports validating the role of EVC variants in the EvC syndrome. The disease correctly segregated in the family members, as all affected members were homozygous, and obligate carriers were heterozygous. Our family is remarkable in highlighting the variable expressivity of the EvC phenotype within the same family, due to a homozygous deletion mutation in the EVC gene. The variable expressivity might be due to the hypomorphic nature of mutation, or the presence of additional variants in modifier genes or in the regulatory regions of the EVC/EVC2 genes.

Artificial intelligence could alert for focal skeleton/bone marrow uptake in Hodgkin's lymphoma patients staged with FDG-PET/CT.

To develop an artificial intelligence (AI)-based method for the detection of focal skeleton/bone marrow uptake (BMU) in patients with Hodgkin's lymphoma (HL) undergoing staging with FDG-PET/CT. The results of the AI in a separate test group were compared to the interpretations of independent physicians. The skeleton and bone marrow were segmented using a convolutional neural network. The training of AI was based on 153 un-treated patients. Bone uptake significantly higher than the mean BMU was marked as abnormal, and an index, based on the total squared abnormal uptake, was computed to identify the focal uptake. Patients with an index above a predefined threshold were interpreted as having focal uptake. As the test group, 48 un-treated patients who had undergone a staging FDG-PET/CT between 2017-2018 with biopsy-proven HL were retrospectively included. Ten physicians classified the 48 cases regarding focal skeleton/BMU. The majority of the physicians agreed with the AI in 39/48 cases (81%) regarding focal skeleton/bone marrow involvement. Inter-observer agreement between the physicians was moderate, Kappa 0.51 (range 0.25-0.80). An AI-based method can be developed to highlight suspicious focal skeleton/BMU in HL patients staged with FDG-PET/CT. Inter-observer agreement regarding focal BMU is moderate among nuclear medicine physicians.

Survey of Post-Cranial Skeletal Pathology in Snakes.

Previous reports on skeletal pathology in captive snakes did not clarify the relationship of lesions to captive or free-ranging status. In this study, post-cranial skeletons from 7,950 captive and free-ranging snakes in nine of the major North American collections were examined macroscopically, microscopically and radiologically for the presence of pathology. Micro-computerized tomography was performed on two skeletons on which surface microscopy failed to provide a definitive diagnosis. Osteomyelitis was identified in the vertebrae of 24 snakes and spondyloarthropathy in one snake. Neoplasia or congenital anomalies were not found. Osteomyelitis was four times as common in Viperidae than in Colubridae and twice as common as in Boidae, independent of captive or free-ranging status. A lytic lesion in the vertebrae of one snake was suggestive of fungal disease. The progression of bone lesions was greater in captive snakes, but the prevalence was independent of captive or free-ranging status. The results of this study indicate that bone alterations, previously proposed as neoplastic disease, in archival snake skeletons were most likely of infectious aetiology, and establish macroscopic examination as a useful technique for characterizing skeletal pathology in snakes.

Transgenic inhibition of interleukin-6 trans-signaling does not prevent skeletal pathologies in mucolipidosis type II mice.

Severe skeletal alterations are common symptoms in patients with mucolipidosis type II (MLII), a rare lysosomal storage disorder of childhood. We have previously reported that progressive bone loss in a mouse model for MLII is caused by an increased number of bone-resorbing osteoclasts, which is accompanied by elevated expression of the cytokine interleukin-6 (IL-6) in the bone microenvironment. In the present study we addressed the question, if pharmacological blockade of IL-6 can prevent the low bone mass phenotype of MLII mice. Since the cellular IL-6 response can be mediated by either the membrane-bound (classic signaling) or the soluble IL-6 receptor (trans-signaling), we first performed cell culture assays and found that both pathways can increase osteoclastogenesis. We then crossed MLII mice with transgenic mice expressing the recombinant soluble fusion protein sgp130Fc, which represents a natural inhibitor of IL-6 trans-signaling. By undecalcified histology and bone-specific histomorphometry we found that high circulating sgp130Fc levels do not affect skeletal growth or remodeling in wild-type mice. Most importantly, blockade of IL-6 trans-signaling did neither reduce osteoclastogenesis, nor increase bone mass in MLII mice. Therefore, our data clearly demonstrate that the bone phenotype of MLII mice cannot be corrected by blocking the IL-6 trans-signaling.

Clinical, radiological and computational studies on two novel GNPTG variants causing mucolipidosis III gamma phenotypes with varying severity.

Mucolipidosis III gamma (ML III γ) is a slowly progressive disorder that affects multiple parts of the body such as the skeleton, joints, and connective tissue structures. It is caused by pathogenic variants in the GNPTG gene that provides instructions for producing the γ subunit of GlcNAc-1-phosphotransferase. In this study we aim to characterize clinical findings and biological insights on two novel GNPTG variants causing ML III γ phenotypes with varying severity. We report on two siblings with ML III γ bearing the previously undescribed c.477C > G (p.Y159*) nonsense variant in a homozygous state as well as a patient with ML III γ bearing the novel c.110 + 19_111-17del variant in a homozygous state. These variants were revealed by whole-exome sequencing and Sanger sequencing, respectively. Their parents, who are heterozygotes for the same mutation, are healthy. The clinical and radiographic presentation of ML III γ in our patients who had c.477C > G (p.Y159*) variant is consistent with a relatively severe form of the disease, which is further supported by a working three-dimensional model of the GlcNAc-1-phosphotransferase γ subunit. On the other hand, it is seen that our patient who carries the c.110 + 19_111-17del variant has a milder phenotype. Our findings help broaden the spectrum of GNPTG variants causing ML III γ and offer structural and mechanistic insights into loss of GlcNAc-1-phosphotransferase γ subunit function.

Tracking down the White Plague. Chapter two: The role of endocranial abnormal blood vessel impressions and periosteal appositions in the paleopathological diagnosis of tuberculous meningitis.

Although endocranial abnormal blood vessel impressions (ABVIs) and periosteal appositions (PAs) have been considered as paleopathological diagnostic criteria for tuberculous meningitis (TBM) based on findings of previous studies, they are not pathognomonic for tuberculosis (TB). Therefore, their utilization in the paleopathological practice can be questioned, especially in consideration that most of the previous studies were not performed on identified skeletal collections but on osteoarchaeological material and did not include statistical data analysis. To fill the aforementioned research gap, for the first time, a macroscopic investigation was conducted on identified pre-antibiotic era skeletons from the Terry Collection. A sample set of 234 individuals who died of TB (TB group) and 193 individuals who died of non-tuberculous causes (NTB group) were examined. The frequency of ABVIs and PAs, as well as other probable TB-related lesions was recorded. To determine the significance of difference (if any) in the frequencies of ABVIs and PAs between the two groups, χ2 testing of our data was performed. We found that ABVIs, PAs, and their co-occurrence with each other and with other probable TB-related lesions were more common in the TB group than in the NTB group. In addition, the χ2 comparative frequencies of ABVIs and PAs revealed a statistically significant difference between individuals who died of TB and individuals who died of NTB causes. Our findings strengthen those of previous studies that ABVIs and PAs are not specific to TBM but can be of tuberculous origin. Therefore, they do have a diagnostic value in the identification of TB in human osteoarchaeological material, especially when they simultaneously occur with other probable TB-related lesions. Their prudent utilization provides paleopathologists with a stronger basis for diagnosing TB and consequently, a more sensitive means of assessing TB frequency in past human populations.